Researcher in the Laboratory

Drug Design and Optimisation

Prof Dr Anna K. H. Hirsch

The Hirsch group adopts a target-based rational design strategy focusing on biologically relevant, often underexplored enzymes, transporters and regulators within bacterial and parasitic pathogens. The group employs a variety of biophysical methods to investigate compound–target interactions and has established several in vitro and cell-based assays for straightforward evaluation of novel anti-infectives and multiparameter optimisation.

Our research and approach

The emergence of drug-resistant strains of human pathogens such as P. aeruginosa, S. aureus or S. pneumoniae is a recognised threat to human health and urgently calls for the development of new antibacterial agents with novel modes of action. The department adopts a target-based strategy focussing on a portfolio of two types of drug targets.

The first group comprises targets which impair vital mechanisms within the bacteria and effectively kill them. One example is the enzyme DXS which plays a crucial role in the methylerythritol phosphate pathway, which is essential for the biosynthesis of universal isoprenoid precursors in many gram-negative pathogens, but absent from humans. The second group comprises targets interfering with pathogenicity and virulence without affecting bacterial viability. These pathoblockers are believed to cause a lower rate of resistance development, whilst leaving the commensal microbiota untouched.

The Hirsch group applies a series of established hit-identification strategies, including structure- and fragment-based drug design, classical medicinal chemistry and virtual screening. In addition, pioneering of innovative protein-templated methods such as dynamic combinatorial chemistry and kinetic target-guided synthesis in terms of the scope of chemical reactions, biological targets and synergistic combinations addresses key bottlenecks. Use of established and innovative techniques to design, synthesize and profile the most promising inhibitors enables efficient subsequent multiparameter optimisation as well as elucidation of the mode of action.

Scientists in the interdisciplinary team have diverse backgrounds such as medicinal chemistry, synthetic organic chemistry, pharmacy, pharmacology, biology or biochemistry, resulting in a diverse skill set.

Team members

Research projects

Due to the rapidly increasing number of pathogenic bacteria being resistant to common antibiotics, the development of new antibacterial agents is urgently needed. To address these problems, the Hirsch group adopts a strategy based on the rational design and synthesis of anti-infectives with novel modes of action. In this context, the group is focusing on a portfolio of biologically relevant, ideally underexplored enzymes, transporters and regulators within bacterial pathogens. These drug targets can be grouped into those that impair vital mechanisms within the bacterium and effectively kill them (e.g., ECF-T, DnaN and DXS) and those that interfere with the pathogenicity and virulence without affecting bacterial viability (e.g., ColH and LasB). 

The group employs a variety of biophysical methods to identify novel hit compounds and to investigate compound–target interactions. Various in vitro and cell-based assays, the generation of in silico data and the co-crystallization of selected compounds with their targets support the straightforward evaluation of novel anti-infectives and their further optimisation by classical and innovative medicinal chemistry approaches.

Below you will find an overview of selected targets we are currently addressing and to which we apply the above-mentioned strategies:


The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake of vitamins by a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of organisms that depend on vitamin uptake, including pathogenic species such as Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecium. As these bacteria cannot synthesize important vitamins such as folic acid, pantothenate and niacin de novo, they depend on ECF transporters to take them up from the environment. Due to this central role in the metabolism of bacteria, ECF transporters are novel potential antimicrobial targets to tackle infection. Recently we identified the first classes of selective antibacterial agents showing promising inhibition of the ECF transporters. We are currently trying to further develop these compounds.

MEP pathway (target: DXS, IspD, IspE):

The methyl erythritol phosphate (MEP) pathway is a rich, underexplored source of anti-infective targets that are absent from humans but essential in many pathogenic bacteria, protozoa and plants. This opens up the possibility of developing highly selective inhibitors that are active against clinically relevant pathogens such as four ESKAPE pathogens: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., all of which have highest priority according to the WHO Global Priority List of antibiotic-resistant bacteria – as well as Mycobacterium tuberculosis and Plasmodium falciparum. In these pathogens, the MEP pathway is the sole source of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The latter are the universal building blocks for the biosynthesis of isoprenoids, a large and diverse class of natural products fulfilling a myriad of indispensable functions. With DXS, IspD, IspE we address three essential enzymes of this pathway. Our best compounds are highly active against the mentioned pathogens and show nanomolar IC50 values.


Antibacterial drugs targeting essential multi-enzyme complexes are less prone to resistance development, since their malfunctioning is hard to bypass. In this context, the bacterial replisome machinery, which consists of at least twelve interacting enzymes that are highly conserved in bacteria, contains several attractive and promising antibacterial targets – including the bacterial β-sliding clamp DnaN. DnaN is a crucial subunit of the DNA polymerase III holoenzyme, preventing polymerase dissociation and enhancing polymerase activity. Furthermore, the β-sliding clamp shows interactions with a variety of other enzymes involved in replication and DNA repair processes. Its important functionality in the replication process and its highly conserved structure across bacterial species and its significant structural divergence to the mammalian counterpart (PCNA) make DnaN an attractive target for the treatment of various pathogens including Mycobacterium tuberculosis. Based on the natural product griselimycin (GM), a known DnaN binder, we adopted a semisynthetic approach, which resulted in a set of GM derivatives with promising antibacterial activities. Furthermore, we identified diverse small organic molecules binding to DnaN. The optimization of the most promising compounds is ongoing.


Clostridia represent a family of ubiquitously occurring gram-positive bacteria comprising perilous pathogens causing serious infectious diseases. The high lethality of these bacteria is related to collagenases, which are crucial for clostridial virulence, given their critical role in colonisation and evasion of host immune defence, acquisition of nutrients, facilitation of dissemination, or tissue damage during infection. The inhibition of these extracellular collagenases is conceptually attractive, as it does not attack the pathogen directly but rather blocks the colonisation and infiltration of the host by the clostridia. Targeting extracellular enzymes has the added benefit that inhibitors do not need to cross the bacterial cell wall, which has been challenging in many cases. Clostridial collagenases are zinc metalloproteinases with a multi-domain organisation, homologues of which are also found in many bacilli. Our group was the first who published compounds showing not only a highly potent inhibition of clostridial and bacillal collagenases (ColH IC50 in nM range) but also a strong selectivity over human MMPs.


Pseudomonas aeruginosa (PA), a highly problematic gram-negative pathogen, which has been assigned critical priority by the WHO, is responsible for many nosocomial infections. The opportunistic pathogen is also commonly found in burns, and in lungs of COPD and cystic fibrosis patients. PA-derived virulence factors play pivotal roles in mechanisms mediating its pathogenesis and infectivity. The strategy to develop “pathoblockers” targeting such virulence factors is expected to leave the commensal microbiome intact and to be less prone to the development of resistance compared to conventional antibiotics. One of the major virulence factors of PA is the extracellular zinc-metalloprotease elastase LasB. LasB substantially contributes to disease progression in PA-infected individuals by facilitating host invasion and immune evasion, and was furthermore reported to be involved in the formation of PA biofilms. Inhibition of LasB is a promising strategy to effectively reduce virulence of PA without affecting viability of the pathogen and the host microbiome. Our most promising LasB inhibitors show nanomolar IC50 values and a promising safety profile.



High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge as Inhibitors of Plasmodium falciparum

Johannsen S, Gierse R, Krüger A, Edwards R, Nanna V, Fontana A, Di Zhu, Masini T, Carvalho L, Poizat M, …, Wrenger C, Hirsch A (2024)

ACS Infect. Dis.DOI: 10.1021/acsinfecdis.3c00670

Hit optimization by dynamic combinatorial chemistry on Streptococcus pneumoniae energy-coupling factor transporter ECF-PanT

Exapicheidou I, Shams A, Ibrahim H, Tsarenko A, Backenköhler M, Hamed M, Diamanti E, Volkamer A, slotboom d, Hirsch A (2024)

Chem. Commun. 60 (7): 870-873DOI: 10.1039/D3CC04738E


Clean Synthetic Strategies to Biologically Active Molecules from Lignin: A Green Path to Drug Discovery

Afanasenko A, Wu X, Santi A, Elgaher W, Kany A, Shafiei R, Schulze M, Schulz T, Haupenthal J, Hirsch A, Barta K (2023)

Angew. Chem. Int. Ed.DOI: 10.1002/anie.202308131

Identification of HuR–RNA Interfering Compounds by Dynamic Combinatorial Chemistry and Fluorescence Polarization

Della Volpe S, Listro R, Ambrosio F, Garbagnoli M, Linciano P, Rossi D, Costa G, Alcaro S, Vasile F, Hirsch A, Collina S (2023)

ACS Med. Chem. Lett.DOI: 10.1021/acsmedchemlett.3c00303

1-deoxy-D-xylulose-5-phosphate synthase from Pseudomonas aeruginosa and Klebsiella pneumoniae reveals conformational changes upon cofactor binding

Hamid R, Adam S, Lacour A, Monjas L, Köhnke J, Hirsch A (2023)

The Journal of biological chemistryDOI: 10.1016/j.jbc.2023.105152

pH-Responsive Dynaplexes as Potent Apoptosis Inductors by Intracellular Delivery of Survivin siRNA

Liu Y, Ashmawy S, Latta L, Weiss A, Kiefer A, Nasr S, Loretz B, Hirsch A, Lee S, Lehr C (2023)

Biomacromolecules 24 (8): 3742-3754DOI: 10.1021/acs.biomac.3c00424

Exploring the Translational Gap of a Novel Class of Escherichia coli IspE Inhibitors

Ropponen H, Diamanti E, Johannsen S, Illarionov B, Hamid R, Jaki M, Sass P, Fischer M, Haupenthal J, Hirsch A (2023)

ChemMedChemDOI: 10.1002/cmdc.202300346

Inhibitors of the Elastase LasB for the treatment of Pseudomonas aeruginosa lung infections

Konstantinovic J, Kany A, Alhayek A, Abdelsamie A, Sikandar A, Voos K, Yao Y, Andreas A, Shafiei R, Loretz B, …, Haupenthal J, Hirsch A (2023)

DOI: 10.26434/chemrxiv-2023-bszcb

Artificial intelligence for natural product drug discovery

Mullowney M, Duncan K, Elsayed S, Garg N, van der Hooft J, Martin N, Meijer D, Terlouw B, Biermann F, Blin K, …, Robinson S, Medema M (2023)

Nat Rev Drug DiscovDOI: 10.1038/s41573-023-00774-7

Thermoresponsive cholesteric liquid-crystal systems doped with terpenoids as drug delivery systems for skin applications

Nesterkina M, Vashchenko O, Vashchenko P, Lisetski L, Kravchenko I, Hirsch A, Lehr C (2023)

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VDOI: 10.1016/j.ejpb.2023.09.002

Design of thiamine analogues for inhibition of thiamine diphosphate (ThDP)-dependent enzymes: Systematic investigation through Scaffold-Hopping and C2-Functionalisation

Chan A, Ho T, Irfan R, Hamid R, Rudge E, Iqbal A, Turner A, Hirsch A., Leeper F (2023)

Bioorganic chemistry 138DOI: 10.1016/j.bioorg.2023.106602

Facile Production of the Pseudomonas aeruginosa Virulence Factor LasB in E. coli for Structure-Based Drug Design

Kolling D, Haupenthal J, Hirsch A, Köhnke J (2023)

ChemBioChemDOI: 10.1002/cbic.202300185

Structure of Mycobacterium tuberculosis 1-Deoxy-D-Xylulose 5-Phosphate Synthase in Complex with Butylacetylphosphonate

Gawriljuk V, Oerlemans R, Gierse R, Jotwani R, Hirsch A, Groves M (2023)

Crystals 13 (5)DOI: 10.3390/cryst13050737

Not Every Hit-Identification Technique Works on 1-Deoxy-d-Xylulose 5-Phosphate Synthase (DXPS): Making the Most of a Virtual Screening Campaign

Johannsen S, Gierse R, Olshanova A, Smerznak E, Laggner C, Eschweiler L, Adeli Z, Hamid R, Alhayek A, Reiling N, Haupenthal J, Hirsch A (2023)

ChemMedChemDOI: 10.1002/cmdc.202200590

Genotoxic and mutational potential of monocyclic terpenoids (carvacrol, carvone and thymol) in Drosophila melanogaster

Nesterkina M, Bilokon S, Alieksieieva T, Kravchenko I, Hirsch A (2023)

Toxicol. Rep. 10DOI: 10.1016/j.toxrep.2023.02.009

Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials

Walesch S, Birkelbach J, Jézéquel G, Haeckl F, Hegemann J, Hesterkamp T, Hirsch A, Hammann P, Müller R (2023)

EMBO reports 24 (1)DOI: 10.15252/embr.202256033

Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle

Hamed M, Abdelsamie A, Rox K, Schütz C, Kany A, Röhrig T, Schmelz S, Blankenfeldt W, Arce-Rodriguez A, Borrero-de Acuña J, …, Hartmann R, Empting M (2023)

Adv. Sci. (Online)DOI: 10.1002/advs.202204443


Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target‐Guided Synthesis

Camberlein V, Fléau C, Sierocki P, Li L, Gealageas R, Bosc D, Guillaume V, Warenghem S, Leroux F, Rosell M, …, Bouvier M, Deprez-Poulain R (2022)

Angew. Chemie 134 (39)DOI: 10.1002/ange.202203560

Synthesis, biological evaluation, and molecular docking studies of aldotetronic acid-based LpxC inhibitors

Wimmer S, Hoff K, Martin B, Grewer M, Denni L, Lascorz Massanet R, Raimondi M, Bülbül E, Melesina J, Hotop S, …, Sippl W, Holl R (2022)

Bioorganic chemistry 131DOI: 10.1016/j.bioorg.2022.106331

Proteoid biodynamers for safe mRNA transfection via pH-responsive nanorods enabling endosomal escape

Lee S, Nasr S, Rasheed S, Liu Y, Hartwig O, Kaya C, Boese A, Koch M, Herrmann J, Müller R, …, Hirsch A, Lehr C (2022)

Journal of controlled release : official journal of the Controlled Release Society 353: 915-929DOI: 10.1016/j.jconrel.2022.12.018

Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation

Ibrahim A, Abdel Gaber S, Fawzi Kabil M, Ahmed-Farid O, Hirsch A, El-Sherbiny I, Nasr M (2022)

Expert Opin. Drug Deliv. 19 (11): 1549-1560DOI: 10.1080/17425247.2022.2139370

Introduction to themed collection on fragment-based drug discovery

Rees D, Hirsch A, Erlanson D (2022)

RSC Med. Chem. 13DOI: 10.1039/D2MD90037H

An Efficient Way to Screen Inhibitors of Energy-Coupling Factor (ECF) Transporters in a Bacterial Uptake Assay

Bousis S, Winkler S, Haupenthal J, Fulco F, Diamanti E, Hirsch A (2022)

International journal of molecular sciences 23 (5)DOI: 10.3390/ijms23052637

Respiratory Syncytial Virus Two-Step Infection Screen Reveals Inhibitors of Early and Late Life Cycle Stages

Sake S, Kosch C, Blockus S, Haid S, Gunesch A, Zhang X, Friesland M, Trummer S, Grethe C, Kühnel A, …, Schulz T, Pietschmann T (2022)

Antimicrobial agents and chemotherapyDOI: 10.1128/aac.01032-22

Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases

Alhayek A, Abdelsamie A, Schönauer E, Camberlein V, Hutterer E, Posselt G, Serwanja J, Blöchl C, Huber C, Haupenthal J, …, Wessler S, Hirsch A (2022)

Journal of medicinal chemistry 65 (19): 12933-12955DOI: 10.1021/acs.jmedchem.2c00785

Discovery of novel drug-like antitubercular hits targeting the MEP pathway enzyme DXPS by strategic application of ligand-based virtual screening

Di Zhu, Johannsen S, Masini T, Simonin C, Haupenthal J, Illarionov B, Andreas A, Awale M, Gierse R, van der Laan T, …, Reymond J, Hirsch A (2022)

Chem. Sci. 13 (36): 10686-10698DOI: 10.1039/D2SC02371G

Screening of Natural Products and Small Molecules Uncovers Novel Coronavirus 1a/1b Frameshifting Inhibitors with Antiviral Properties

Kibe A, Elgaher W, Rand U, Zimmer M, Kany A, Hermann J, Müller R, Cicin-Sain L, Hirsch A, Caliskan N (2022)

SSRN JournalDOI: 10.2139/ssrn.4157446

Design, Synthesis, Antimicrobial Activity, and Molecular Docking of Some New Diclofenac Derivatives

Tolba M, Hamed M, Sayed M, Kamal El-Dean A, Abdel-Mohsen S, Ibrahim O, Elgaher W, Hirsch A, Saddik A (2022)

Polycyclic Aromatic Compounds: 1-16DOI: 10.1080/10406638.2022.2102661

Structural analysis of 1-deoxy-D-xylulose 5-phosphate synthase from Pseudomonas aeruginosa and Klebsiella pneumoniae reveals conformational changes upon cofactor binding

Hamid R, Adam S, Lacour A, Gomez L, Hirsch A (2022)

bioRxivDOI: 10.1101/2022.07.04.498669

Identification of RAD51-BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry

Bagnolini G, Balboni B, Schipani F, Gioia D, Veronesi M, Franco F, Kaya C, Jumde R, Ortega J, Girotto S, …, Roberti M, Cavalli A (2022)

ACS Med. Chem. Lett. 13 (8): 1262-1269DOI: 10.1021/acsmedchemlett.2c00063

The Structures and Binding Modes of Small-Molecule Inhibitors of Pseudomonas aeruginosa Elastase LasB

Camberlein V, Jézéquel G, Haupenthal J, Hirsch A (2022)

Antibiotics 11 (8)DOI: 10.3390/antibiotics11081060

Transferring Microclusters of P. aeruginosa Biofilms to the Air-Liquid Interface of Bronchial Epithelial Cells for Repeated Deposition of Aerosolized Tobramycin

Horstmann J, Laric A, Boese A, Yildiz D, Röhrig T, Empting M, Frank N, Krug D, Müller R, Schneider-Daum N, Souza Carvalho-Wodarz C, Lehr C (2022)

ACS infectious diseases 8 (1): 137-149DOI: 10.1021/acsinfecdis.1c00444

Structure-Guided Optimization of Small-Molecule Folate Uptake Inhibitors Targeting the Energy-Coupling Factor Transporters

Kiefer A, Bousis S, Hamed M, Diamanti E, Haupenthal J, Hirsch A (2022)

J. Med. Chem.DOI: 10.1021/acs.jmedchem.1c02114

Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism

Chen F, Elgaher W, Winterhoff M, Büssow K, Waqas F, Graner E, Pires-Afonso Y, Casares Perez L, La Vega L, Sahini N, …, Hirsch A, Pessler F (2022)

Nature metabolism 4 (5): 534-546DOI: 10.1038/s42255-022-00577-x

Targeting Extracellular Bacterial Proteases for the Development of Novel Antivirulence Agents

Kaya C, Hirsch A (2022)

Chimia 76 (5)DOI: 10.2533/chimia.2022.402

Design and Synthesis of Novel Bis-Imidazolyl Phenyl Butadiyne Derivatives as HCV NS5A Inhibitors

Hamdy J, Emadeldin N, Hamed M, Frakolaki E, Katsamakas S, Vassilaki N, Zoidis G, Hirsch A, Abdel-Halim M, Abadi A (2022)

Pharmaceuticals 15 (5)DOI: 10.3390/ph15050632

First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization

Gierse R, Oerlemans R, Reddem E, Gawriljuk V, Alhayek A, Baitinger D, Jakobi H, Laber B, Lange G, Hirsch A, Groves M (2022)

Sci. Rep. 12 (1)DOI: 10.1038/s41598-022-11205-9

N-Aryl-2-iso-butylmercaptoacetamides: the discovery of highly potent and selective inhibitors of Pseudomonas aeruginosa virulence factor LasB and Clostridium histolyticum virulence factor ColH

Voos K, Yahiaoui S, Konstantinovic J, Schönauer E, Alhayek A, Sikandar A, Si Chaib K, Ramspoth T, Rox K, Haupenthal J, …, Ducho C, Hirsch A (2022)

ChemRxivDOI: 10.26434/chemrxiv-2022-fjrqr

Structure-Based Design of α-Substituted Mercaptoacetamides as Inhibitors of the Virulence Factor LasB from Pseudomonas aeruginosa

Kaya C, Walter I, Alhayek A, Shafiei R, Jézéquel G, Andreas A, Konstantinovic J, Schönauer E, Sikandar A, Haupenthal J, …, Hartmann R, Hirsch A (2022)

ACS Infect. Dis.DOI: 10.1021/acsinfecdis.1c00628

N-Aryl Mercaptopropionamides as Broad-Spectrum Inhibitors of Metallo-β-Lactamases

Kaya C, Konstantinovic J, Kany A, Andreas A, Kramer J, Brunst S, Weizel L, Rotter M, Frank D, Yahiaoui S, …, Wichelhaus T, Hirsch A (2022)

Journal of medicinal chemistry 65 (5): 3913-3922DOI: 10.1021/acs.jmedchem.1c01755

Metabolic profiling of S-praziquantel: Structure elucidation using the crystalline sponge method in combination with mass spectrometry and nuclear magnetic resonance

Rosenberger L, Jenniches J, Essen C, Khutia A, Kühn C, Marx A, Georgi K, Hirsch A, Hartmann R, Badolo L (2022)

Drug metabolism and disposition: the biological fate of chemicalsDOI: 10.1124/dmd.121.000663

Inhibition of Collagenase Q1 of Bacillus cereus as a Novel Antivirulence Strategy for the Treatment of Skin‐Wound Infections

Alhayek A, Khan E, Schönauer E, Däinghaus T, Shafiei R, Voos K, Han M, Ducho C, Posselt G, Wessler S, …, del Campo A, Hirsch A (2022)

Adv. Therap.DOI: 10.1002/adtp.202100222

Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor

Drost M, Diamanti E, Fuhrmann K, Goes A, Shams A, Haupenthal J, Koch M, Hirsch A, Fuhrmann G (2022)

Pharmaceutics 14 (1)DOI: 10.3390/pharmaceutics14010004

Inhibitors of Pseudomonas aeruginosa virulence factor LasB

Ducho C, Hartmann R, Haupenthal J, Hirsch A, Kany A, Kaya C, Konstantinovic J, Voos K, Walter I, Yahiaoui S, …, Jumde R, Kiefer A (2022)

Patent A61K31/095; A61K31/10; A61K31/167; A61K31/4184; A61K31/426; A61K31/428; A61K31/4406; A61P31/04; C07C323/60; C07D213/74; C07D235/30; C07D277/46; C07D277/82; C07D333/36; C07F9/38; C07F9/40; (WO2022043322A1)


Citatronic Acid and Derivates thereof for use as a medicament

Pessler F., Chen F., Winterhoff M., Büssow K., Blankenfeldt W., Hirsch A. K. H., Elgaher W (2021)

Patent (WO2022223778, 2022)

N-Phenyl-3-Mercaptopropanamide Derivatives as Metallo-Beta-Lactamase Inhibitors for the Treatment of Bacterial Infections

Hartmann R, Konstantinovic J, Haupenthal J, Hirsch A, Kany A, Kaya C, Yahiaoui S, Wichelhaus T, Proschak E (2021)

Patent A61K31/5375; A61P31/04; C07C233/15; C07C233/25; C07C233/33; C07C233/43; C07C233/54; C07C319/02; C07C323/52; C07D295/22; (‌‌WO2021191219A1)

New PqsR Inverse Agonist

Schütz C, Empting M, Ahmed S, Hamed M, Hartmann R, Röhrig T, Kany A, Hirsch A (2021)

Patent A61K31/4439; A61K31/506; A61P31/04; C07D401/12; C07D403/12; (WO2021136803A1)

Novel PqsR Inverse Agonists

Hamed M, Ahmed S, Empting. M., Schütz C, Hartmann R, Röhrig T, Kany A, Hirsch A (2021)

Patent A61K31/4439; A61P31/04; C07D401/14; C07D417/14; (WO2021136805A1)

Towards the sustainable discovery and development of new antibiotics

Miethke M, Pieroni M, Weber T, Brönstrup M, Hammann P, Halby L, Arimondo P, Glaser P, Aigle B, Bode H, …, Moser H, Müller R (2021)

Nature reviews. Chemistry 5 (10): 726-749DOI: 10.1038/s41570-021-00313-1

Targeting the IspD Enzyme in the MEP Pathway: Identification of a Novel Fragment Class

Diamanti E, Hamed M, Lacour A, Bravo P, Illarionov B, Fischer M, Rottmann M, Witschel M, Hirsch A (2021)

ChemMedChemDOI: 10.1002/cmdc.202100679

Substrate-Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors

Kaya C, Walter I, Yahiaoui S, Sikandar A, Alhayek A, Konstantinovic J, Kany A, Haupenthal J, Köhnke J, Hartmann R, Hirsch A (2021)

Angewandte Chemie (International ed. in English)DOI: 10.1002/anie.202112295

Targeting the energy-coupling factor (ECF) transporters: identification of new tool compounds

Diamanti E, Setyawati I, Bousis S, Souza P, mojas l, Swier l, Haupenthal J, Gibson P, Volz C, stanek w, …, slotboom d, Hirsch A (2021)

ChemRxivDOI: 10.26434/chemrxiv-2021-xq08b-v2

Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier

Abdallah M, Hamed M, Frakolaki E, Katsamakas S, Vassilaki N, Bartenschlager R, Zoidis G, Hirsch A, Abdel-Halim M, Abadi A (2021)

European journal of medicinal chemistryDOI: 10.1016/j.ejmech.2021.114034

Unveiling Adatoms in On-Surface Reactions: Combining Scanning Probe Microscopy with van't Hoff Plots

Moreno-López J, Pérez Paz A, Gottardi S, Solianyk L, Li J, Monjas L, Hirsch A, Mowbray D, Stöhr M (2021)

The journal of physical chemistry. C, Nanomaterials and interfaces 125 (18): 9847-9854DOI: 10.1021/acs.jpcc.1c03134

1st Spring Virtual Meeting on Medicinal Chemistry

Sousa M, Marques M, Faustino M (2021)

Chemistry Proceedings 4 (1)DOI: 10.3390/chemproc2021004001

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as sphingosine kinase 1 inhibitor

Khairat S, Omar M, Ragab F, Roy S, Turab Naqvi A, Abdelsamie A, Hirsch A, Galal S, Hassan M, El Diwani H (2021)

Archiv der Pharmazie 354 (9)DOI: 10.1002/ardp.202100080

Identification of N,N-arylalkyl-picolinamide derivatives targeting the RNA-binding protein HuR, by combining biophysical fragment-screening and molecular hybridization

Della Volpe S, Linciano P, Listro R, Tumminelli E, Amadio M, Bonomo I, Elgaher W, Adam S, Hirsch A, Boeckler F, …, Rossi D, Collina S (2021)

Bioorganic chemistry 116DOI: 10.1016/j.bioorg.2021.105305

Expanding the Myxochelin Natural Product Family by Nicotinic Acid Containing Congeners

Frank N, Széles M, Akone S, Rasheed S, Hüttel S, Frewert S, Hamed M, Herrmann J, Schuler S, Hirsch A, Müller R (2021)

Molecules 26 (16)DOI: 10.3390/molecules26164929

N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB from Pseudomonas aeruginosa

Yahiaoui S, Voos K, Haupenthal J, Wichelhaus T, Frank D, Weizel L, Rotter M, Brunst S, Kramer J, Proschak E, Ducho C, Hirsch A (2021)

RSC Med. Chem.DOI: 10.1039/D1MD00187F

Crystalline sponge affinity screening: A fast tool for soaking condition optimization without the need of X-ray diffraction analysis

Rosenberger L, Essen C, Khutia A, Kühn C, Georgi K, Hirsch A, Hartmann R, Badolo L (2021)

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 164DOI: 10.1016/j.ejps.2021.105884

A New PqsR Inverse Agonist Potentiates Tobramycin Efficacy to Eradicate Pseudomonas aeruginosa Biofilms

Schütz C, Ho D, Hamed M, Abdelsamie A, Röhrig T, Herr C, Kany A, Rox K, Schmelz S, Siebenbürger L, …, Lehr C, Empting M (2021)

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 (12)DOI: 10.1002/advs.202004369

“Clicking“ fragment leads to novel dual-binding cholinesterase inhibitors

Moleda Z, Zawadzka A, Czarnocki Z, Monjas L, Hirsch A, Budzianowski A, Maurin J (2021)

Bioorg Med ChemDOI: 10.1016/j.bmc.2021.116269

Phosphonate as a Stable Zinc‐Binding Group for “Pathoblocker” Inhibitors of Clostridial Collagenase H (ColH) (ChemMedChem 8/2021)

Voos K, Schönauer E, Alhayek A, Haupenthal J, Andreas A, Müller R, Hartmann R, Brandstetter H, Hirsch A, Ducho C (2021)

ChemMedChem 16 (8): 1198-1198DOI: 10.1002/cmdc.202100229

Hit-optimization using target-directed dynamic combinatorial chemistry: Development of inhibitors of the anti-infective target 1-deoxy-D-xylulose-5-phosphate synthase

Jumde R, Guadigni M, Gierse R, Alhayek A, Di Zhu, Hamid Z, Johannsen S, Elgaher W, Neusens P, Nehls C, …, Reiling N, Hirsch A (2021)

Chemical ScienceDOI: 10.1039/D1SC00330E

Search for the Active Ingredients from a 2-Aminothiazole DMSO Stock Solution with Antimalarial Activity

Ropponen H, Bader C, Diamanti E, Illarionov B, Rottmann M, Fischer M, Witschel M, Müller R, Hirsch A (2021)

ChemMedChem 16 (13): 2089-2093DOI: 10.1002/cmdc.202100067

Mastering the Gram-Negative Bacterial Barrier - Chemical Approaches to Increase Bacterial Bioavailability of Antibiotics

Ropponen H, Richter R, Hirsch A, Lehr C (2021)

Advanced Drug Delivery ReviewsDOI: 10.1016/j.addr.2021.02.014

Assessment of the rules related to gaining activity against Gram-negative bacteria

Ropponen H, Diamanti E, Siemens A, Illarionov B, Haupenthal J, Fischer M, Rottmann M, Witschel M, Hirsch A (2021)

RSC Med. Chem.DOI: 10.1039/D0MD00409J

Enhancing glycan stability via site-selective fluorination: modulating substrate orientation by molecular design

Axer A, Jumde R, Adam S, Faust A, Schäfers M, Fobker M, Koehnke J, Hirsch A, Gilmour R (2021)

Chem. Sci. 12 (4): 1286-1294DOI: 10.1039/D0SC04297H

Identification of a 1-deoxy-D-xylulose-5-phosphate synthase (DXS) mutant with improved crystallographic properties

Gierse R, Reddem E, Alhayek A, Baitinger D, Hamid Z, Jakobi H, Laber B, Lange G, Hirsch A, Groves (2021)

Biochemical and Biophysical Research Communications 539DOI: 10.1016/j.bbrc.2020.12.069


A hydrogel-based in vitro assay for the fast prediction of antibiotic accumulation in Gram-negative bacteria

Richter R, Kamal M, García-Rivera M, Kaspar J, Junk M, Elgaher W, Srikakulam S, Gress A, Beckmann A, Grißmer A, …, Schneider-Daum N, Lehr C (2020)

Materials today. Bio 8DOI: 10.1016/j.mtbio.2020.100084

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Murgia X, Kany A, Herr C, Ho D, Rossi C, Bals R, Lehr C, Hirsch A, Hartmann R, Empting M, Röhrig T (2020)

Scientific Reports 10 (1)DOI: 10.1038/s41598-020-73459-5

Semisynthesis and biological evaluation of amidochelocardin derivatives as broad-spectrum antibiotics

Grandclaudon C, Birudukota N, Elgaher W, Jumde R, Yahiaoui S, Arisetti N, Hennessen F, Hüttel S, Stadler M, Herrmann J, …, Hirsch A, Brönstrup M (2020)

European journal of medicinal chemistry 188DOI: 10.1016/j.ejmech.2019.112005

Discovery of Small-Molecule Stabilizers of 14-3-3 Protein-Protein Interactions via Dynamic Combinatorial Chemistry

Hartman A, Elgaher W, Hertrich N, Andrei S, Ottmann C, Hirsch A (2020)

ACS medicinal chemistry letters 11 (5): 1041-1046DOI: 10.1021/acsmedchemlett.9b00541

Evaluation of Bacterial RNA Polymerase Inhibitors in a Staphylococcus aureus-Based Wound Infection Model in SKH1 Mice

Haupenthal J, Kautz Y, Elgaher W, Pätzold L, Röhrig T, Laschke M, Tschernig T, Hirsch A, Molodtsov V, Murakami K, Hartmann R, Bischoff M (2020)

ACS infectious diseases 6 (10): 2573-2581DOI: 10.1021/acsinfecdis.0c00034

François Diederich – In Memoriam**

Hof F, Hirsch A (2020)

ChemMedChemDOI: 10.1002/cmdc.202000920

Protein‐Templated Hit Identification through an Ugi Four‐Component Reaction

Federica Mancini, M. Yagiz Unver, Walid A. M. Elgaher, Varsha R. Jumde, Alaa Alhayek, Peer Lukat, Jennifer Herrmann, Martin D. Witte, Matthias Köck, Wulf Blankenfeldt, Rolf Müller, Hirsch A (2020)

Chemistry – A European Journal 26 (64)DOI: 10.1002/chem.202086462

7-Hydroxycoumarins are Affinity-based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor

Xiao Z, Chen D, Song S, van der Vlag R, van der Wouden P, van Merkerk R, Cool R, Hirsch A, Melgert B, Quax W, Poelarends G, Dekker F (2020)

Journal of medicinal chemistryDOI: 10.1021/acs.jmedchem.0c01160

pH-Dependent morphology and optical properties of lysine-derived molecular biodynamers

Lee S, Kaya C, Jang H, Koch M, Loretz B, Buhler E, Lehr C, Hirsch A (2020)

Mater. Chem. Front. 4 (3): 905-909DOI: 10.1039/C9QM00651F

Rapid Discovery of Aspartyl Protease Inhibitors Using an Anchoring Approach

Konstantinidou M, Magari F, Sutanto F, Haupenthal J, Jumde R, Ünver M, Heine A, Camacho C, Hirsch A, Klebe G, Dömling A (2020)

ChemMedChem 15 (8): 680-684DOI: 10.1002/cmdc.202000024

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

Hollenhorst M, Jurastow I, Nandigama R, Appenzeller S, Li L, Vogel J, Wiederhold S, Althaus M, Empting M, Altmüller J, …, Saliba A, Krasteva-Christ G (2020)

FASEB j. 34 (1): 316-332DOI: 10.1096/fj.201901314RR

Optimized Inhibitors of MDM2 via an Attempted Protein‐Templated Reductive Amination

Vlag R, Yagiz Unver M, Felicetti T, Twarda-Clapa A, Kassim F, Ermis C, Neochoritis C, Musielak B, Labuzek B, Dömling A, Holak T, Hirsch A (2020)

ChemMedChem 15 (4): 370-375DOI: 10.1002/cmdc.201900574

Synthesis and Biological Evaluation of Novel 2-Substituted ­Analogues of (–)-Pentenomycin I

Zisopoulou S, Bousis S, Haupenthal J, Herrmann J, Müller R, Hirsch A, Komiotis D, Gallos J, Stathakis C (2020)

Synlett 31 (05): 475-481DOI: 10.1055/s-0039-1690772

BOPC1 Enantiomers Preparation and HuR Interaction Study. From Molecular Modeling to a Curious DEEP-STD NMR Application

Della Volpe S, Listro R, Parafioriti M, Di Giacomo M, Rossi D, Ambrosio F, Costa G, Alcaro S, Ortuso F, Hirsch A, Vasile F, Collina S (2020)

ACS medicinal chemistry letters 11 (5): 883-888DOI: 10.1021/acsmedchemlett.9b00659

Validating the 1,2-Difluoro Motif As a Hybrid Bioisostere of CF3 and Et Using Matrix Metalloproteinases As Structural Probes

Erdeljac N, Thiehoff C, Jumde R, Daniliuc C, Höppner S, Faust A, Hirsch A, Gilmour R (2020)

Journal of medicinal chemistry 63 (11): 6225-6237DOI: 10.1021/acs.jmedchem.0c00648

Protein‐Templated Hit Identification via an Ugi Four‐Component Reaction

Mancini F, Unver M, Elgaher W, Jumde V, Alhayek A, Lukat P, Herrmann J, Witte M, Köck M, Blankenfeldt W, Müller R, Hirsch A (2020)

Chem. Eur. J.DOI: 10.1002/chem.202002250

N -Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases

Konstantinovic J, Yahiaoui S, Alhayek A, Haupenthal J, Schönauer E, Andreas A, Kany A, Müller R, Koehnke J, Berger F, …, Brandstetter H, Hirsch A (2020)

J. Med. Chem. 63 (15): 8359-8368DOI: 10.1021/acs.jmedchem.0c00584

Flotillin-mediated membrane fluidity controls peptidoglycan synthesis and MreB movement

Zielinska A, Savietto A, Sousa Borges A, Martinez D, Berbon M, Roelofsen J, Hartman A, Boer R, van der Klei I, Hirsch A, …, Bramkamp M, Scheffers D (2020)

eLife 9DOI: 10.7554/eLife.57179

Potential Dental Biofilm Inhibitors: Dynamic Combinatorial Chemistry Affords Sugar-Based Molecules that Target Bacterial Glucosyltransferase

Hartman A, Jumde V, Elgaher W, Te Poele E, Dijkhuizen L, Hirsch A (2020)

ChemMedChemDOI: 10.1002/cmdc.202000222

A rapid synthesis of low-nanomolar divalent LecA inhibitors in four linear steps from d -galactose pentaacetate

Zahorska E, Kuhaudomlarp S, Minervini S, Yousaf S, Lepsik M, Kinsinger T, Hirsch A, Imberty A, Titz A (2020)

Chem. Commun. 56 (62): 8822-8825DOI: 10.1039/d0cc03490h

Novel PqsR Inverse Agonists

Hamed M, Ahmed S, Empting. M., Schütz C, Hartmann R, Röhrig T, Kany A, Hirsch A (2020)

Patent (EP20150119)


Energy-Coupling Factor Transporters as Novel Antimicrobial Targets

Bousis S, Setyawati I, Diamanti E, Slotboom D, Hirsch A (2019)

Advanced Therapeutics, 2, 1800066DOI: 10.1002/ADTP.201800066

Protein-Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol

Hartman A, Gierse R, Hirsch A (2019)

European journal of organic chemistry 2019 (22): 3581-3590DOI: 10.1002/ejoc.201900327

Concepts and Core Principles of Fragment-Based Drug Design

Kirsch P, Hartman A, Hirsch A, Empting M (2019)

Molecules (Basel, Switzerland) 24 (23)DOI: 10.3390/molecules24234309

Comparing the Self-Assembly of Sexiphenyl-Dicarbonitrile on Graphite and Graphene on Cu(111)

Schmidt N, Li J, Gottardi S, Moreno-Lopez J, Enache M, Monjas L, van der Vlag R, Havenith R, Hirsch A, Stöhr M (2019)

Chem. Eur. J. 25 (19): 5065-5070DOI: 10.1002/chem.201806312

Inverting Small Molecule–Protein Recognition by the Fluorine Gauche Effect: Selectivity Regulated by Multiple H→F Bioisosterism

Bentler P, Bergander K, Daniliuc C, Mück-Lichtenfeld C, Jumde R, Hirsch A, Gilmour R (2019)

Angewandte Chemie (International ed. in English) 58 (32): 10990-10994DOI: 10.1002/anie.201905452

Spray-drying of inhalable, multifunctional formulations for the treatment of biofilms formed in cystic fibrosis

Lababidi N, Ofosu Kissi E, Elgaher W, Sigal V, Haupenthal J, Schwarz B, Hirsch A, Rades T, Schneider M (2019)

Journal of Controlled Release 314: 62-71DOI: 10.1016/j.jconrel.2019.10.038

From Wood to Tetrahydro-2-benzazepines in Three Waste-Free Steps: Modular Synthesis of Biologically Active Lignin-Derived Scaffolds

Elangovan S, Afanasenko A, Haupenthal J, Sun Z, Liu Y, Hirsch A, Barta K (2019)

ACS Cent. Sci. 5 (10): 1707-1716DOI: 10.1021/acscentsci.9b00781

Surface state tunable energy and mass renormalization from homothetic quantum dot arrays

Piquero-Zulaica I, Li J, Abd El-Fattah Z, Solianyk L, Gallardo I, Monjas L, Hirsch A, Arnau A, Ortega J, Stöhr M, Lobo-Checa J (2019)

Nanoscale 11 (48): 23132-23138DOI: 10.1039/c9nr07365e

Novel Compounds Targeting the RNA-Binding Protein HuR. Structure-Based Design, Synthesis, and Interaction Studies

Della Volpe S, Nasti R, Queirolo M, Unver M, Jumde V, Dömling A, Vasile F, Potenza D, Ambrosio F, Costa G, …, Hirsch A, Collina S (2019)

ACS Med. Chem. Lett. 10 (4): 615-620DOI: 10.1021/acsmedchemlett.8b00600

A combinatorial approach for the discovery of drug-like inhibitors of 15-lipoxygenase-1

van der Vlag R, Guo H, Hapko U, Eleftheriadis N, Monjas L, Dekker F, Hirsch A (2019)

European journal of medicinal chemistry 174: 45-55DOI: 10.1016/j.ejmech.2019.04.021

Rational Adaptation of L3MBTL1 Inhibitors to Create Small-Molecule Cbx7 Antagonists

Simhadri C, Daze K, Douglas S, Milosevich N, Monjas L, Dev A, Brown T, Hirsch A, Wulff J, Hof F (2019)

ChemMedChem 14 (15): 1444-1456DOI: 10.1002/cmdc.201900021

Low-Dimensional Metal-Organic Coordination Structures on Graphene

Li J, Solianyk L, Schmidt N, Baker B, Gottardi S, Moreno Lopez J, Enache M, Monjas L, van der Vlag R, Havenith R, Hirsch A, Stöhr M (2019)

The journal of physical chemistry. C, Nanomaterials and interfaces 123 (20): 12730-12735DOI: 10.1021/acs.jpcc.9b00326

Novel 15-Lipoxygenase-1 Inhibitor Protects Macrophages from Lipopolysaccharide-Induced Cytotoxicity

Guo H, Verhoek I, Prins G, van der Vlag R, van der Wouden P, van Merkerk R, Quax W, Olinga P, Hirsch A, Dekker F (2019)

Journal of medicinal chemistry 62 (9): 4624-4637DOI: 10.1021/acs.jmedchem.9b00212

Replacement of an Indole Scaffold Targeting Human 15-Lipoxygenase-1 Using Combinatorial Chemistry

Prismawan D, van der Vlag R, Guo H, Dekker F, Hirsch A (2019)

HCA 102 (5)DOI: 10.1002/hlca.201900040

Reversible immobilization of a protein to a gold surface through multiple host-guest interactions

Schwarz D, Elgaher W, Hollemeyer K, Hirsch A, Wenz G (2019)

J. Mater. Chem. B 7 (40): 6148-6155DOI: 10.1039/c9tb00560a


Trendbericht Biochemie 2017: Proteinvermittelte dynamische kombinatorische Chemie

Hirsch A (2018)

Nachr. Chem. 66 (3): 281-283DOI: 10.1002/nadc.20184071734

Druggability Assessment of Targets Used in Kinetic Target-Guided Synthesis

Unver M, Gierse R, Ritchie H, Hirsch A (2018)

Journal of medicinal chemistry 61 (21): 9395-9409DOI: 10.1021/acs.jmedchem.8b00266

Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor

Marcozzi A, Masini T, Di Zhu, Pesce D, Illarionov B, Fischer M, Herrmann A, Hirsch A (2018)

ChemBioChem 19 (1): 58-65DOI: 10.1002/cbic.201700402

Lipid-DNAs as Solubilizers of m THPC

Liu Y, de Vries J, Liu Q, Hartman A, Wieland G, Wieczorek S, Börner H, Wiehe A, Buhler E, Stuart M, …, Herrmann A, Hirsch A (2018)

Chem. Eur. J. 24 (4): 798-802DOI: 10.1002/chem.201705206

Glucansucrase (mutant) enzymes from Lactobacillus reuteri 180 efficiently transglucosylate Stevia component rebaudioside A, resulting in a superior taste

Te Poele E, Devlamynck T, Jäger M, Gerwig G, van de Walle D, Dewettinck K, Hirsch A, Kamerling J, Soetaert W, Dijkhuizen L (2018)

Sci Rep 8 (1)DOI: 10.1038/s41598-018-19622-5

Delivery system for budesonide based on lipid-DNA

Liu Y, Bos I, Oenema T, Meurs H, Maarsingh H, Hirsch A (2018)

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 130: 123-127DOI: 10.1016/j.ejpb.2018.06.012

Dynamic Proteoids Generated From Dipeptide-Based Monomers

Liu Y, Stuart M, Buhler E, Hirsch A (2018)

Macromolecular rapid communications 39 (13)DOI: 10.1002/marc.201800099

Design and Synthesis of Bioisosteres of Acylhydrazones as Stable Inhibitors of the Aspartic Protease Endothiapepsin

Jumde V, Mondal M, Gierse R, Unver M, Magari F, van Lier R, Heine A, Klebe G, Hirsch A (2018)

ChemMedChem 13 (21): 2266-2270DOI: 10.1002/cmdc.201800446

Exploration of ligand binding modes towards the identification of compounds targeting HuR: a combined STD-NMR and Molecular Modelling approach

Vasile F, Della Volpe S, Ambrosio F, Costa G, Unver M, Zucal C, Rossi D, Martino E, Provenzani A, Hirsch A, …, Potenza D, Collina S (2018)

Sci Rep 8 (1)DOI: 10.1038/s41598-018-32084-z

Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments

Lozinska I, Swierczynska A, Moleda Z, Hartman A, Hirsch A, Czarnocki Z (2018)

Archiv der Pharmazie 351 (11)DOI: 10.1002/ardp.201800194


Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

Liu Y, Lehn J, Hirsch A (2017)

Accounts of chemical research 50 (2): 376-386DOI: 10.1021/acs.accounts.6b00594

DXS as a target for structure-based drug design

Gierse R, Redeem E, Diamanti E, Wrenger C, Groves M, Hirsch A (2017)

Future medicinal chemistry 9 (11): 1277-1294DOI: 10.4155/fmc-2016-0239

Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3

Hartman A, Hirsch A (2017)

European journal of medicinal chemistry 136DOI: 10.1016/j.ejmech.2017.04.058

Compounds Interfering with Embryonic Lethal Abnormal Vision (ELAV) Protein-RNA Complexes: An Avenue for Discovering New Drugs

Nasti R, Rossi D, Amadio M, Pascale A, Unver M, Hirsch A, Collina S (2017)

Journal of medicinal chemistry 60 (20): 8257-8267DOI: 10.1021/acs.jmedchem.6b01871

Fine-tuning Nanocarriers Specifically toward Cargo: A Competitive Study on Solubilizing Related Photosensitizers for Photodynamic Therapy

Wieczorek S, Remmler D, Masini T, Kochovski Z, Hirsch A, Börner H (2017)

Bioconjugate chemistry 28 (3): 760-767DOI: 10.1021/acs.bioconjchem.6b00549

Pentapeptide‐rich peptidoglycan at the Bacillus subtilis cell‐division site

Morales Angeles D, Liu Y, Hartman A, Borisova M, Sousa Borges A, Kok N, Beilharz K, veening j, Mayer C, Hirsch A, Scheffers D (2017)

Molecular microbiology 104 (2): 319-333DOI: 10.1111/mmi.13629

Bicyclic enol cyclocarbamates inhibit penicillin-binding proteins

Dockerty P, Edens J, Tol M, Morales Angeles D, Domenech A, Liu Y, Hirsch A, veening j, Scheffers D, Witte M (2017)

Organic & biomolecular chemistry 15 (4): 894-910DOI: 10.1039/c6ob01664b

Designed Spiroketal Protein Modulation

Scheepstra M, Andrei S, Unver M, Hirsch A, Leysen S, Ottmann C, Brunsveld L, Milroy L (2017)

Angewandte Chemie (International ed. in English) 56 (20): 5480-5484DOI: 10.1002/anie.201612504

Insight into the complete substrate-binding pocket of ThiT by chemical and genetic mutations

Swier L, Monjas L, Reeßing F, Oudshoorn R, Aisyah, Primke T, Bakker M, van Olst E, Ritschel T, Faustino I, …, Hirsch A, Slotboom D (2017)

MedChemComm 8 (5): 1121-1130DOI: 10.1039/c7md00079k

Saccharide-Containing Dynamic Proteoids

Liu Y, Stuart M, Witte M, Buhler E, Hirsch A (2017)

Chemistry (Weinheim an der Bergstrasse, Germany) 23 (64): 16162-16166DOI: 10.1002/chem.201703584

Dynamic Combinatorial Chemistry to Identify Binders of ThiT, an S-Component of the Energy-Coupling Factor Transporter for Thiamine

Monjas L, Swier L, Setyawati I, slotboom d, Hirsch A (2017)

ChemMedChem 12 (20): 1693-1696DOI: 10.1002/cmdc.201700440


Design and synthesis of thiamine analogues to study their binding to the ECF transporter for thiamine in bacteria

Monjas L, Swier L, Voogd A, Oudshoorn R, Hirsch A, Slotboom D (2016)

Med. Chem. Commun. 7 (5): 966-971DOI: 10.1039/C6MD00022C

Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site

Masini T, Birkaya B, van Dijk S, Mondal M, Hekelaar J, Jäger M, van Terwisscha Scheltinga A, Patel M, Hirsch A, Moman E (2016)

Journal of enzyme inhibition and medicinal chemistry 31 (sup4): 170-175DOI: 10.1080/14756366.2016.1201812

Proteoid Dynamers with Tunable Properties

Liu Y, Stuart M, Buhler E, Lehn J, Hirsch A (2016)

DOI: 10.1002/ADFM.201601612

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

Mondal M, Radeva N, Fanlo-Virgós H, Otto S, Klebe G, Hirsch A (2016)

Angewandte Chemie (International ed. in English) 55 (32): 9422-6DOI: 10.1002/anie.201603074

Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

Mondal M, Unver M, Pal A, Bakker M, Berrier S, Hirsch A (2016)

Chem. Eur. J. 22 (42): 14826-14830DOI: 10.1002/chem.201603001


Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets

Mondal M, Hirsch A (2015)

Chemical Society reviews 44 (8): 2455-88DOI: 10.1039/c4cs00493k

Fighting malaria: structure-guided discovery of nonpeptidomimetic plasmepsin inhibitors

Huizing A, Mondal M, Hirsch A (2015)

Journal of medicinal chemistry 58 (13): 5151-63DOI: 10.1021/jm5014133

Harnessing dynamic combinatorial chemistry in the search for new ligands for protein targets

Monjas L, Hirsch A (2015)

Future medicinal chemistry 7 (16): 2095-8DOI: 10.4155/fmc.15.146

Combinatorial screening for specific drug solubilizers with switchable release profiles

Wieczorek S, Vigne S, Masini T, Ponader D, Hartmann L, Hirsch A, Börner H (2015)

Macromolecular Bioscience 15 (1): 82-9DOI: 10.1002/mabi.201400443

Structure-based design of potent small-molecule binders to the S-component of the ECF transporter for thiamine

Swier L, Monjas L, Guskov A, Voogd A, Erkens G, slotboom d, Hirsch A (2015)

ChemBioChem 16 (5): 819-26DOI: 10.1002/cbic.201402673

Fragment growing exploiting dynamic combinatorial chemistry of inhibitors of the aspartic protease endothiapepsin

Mondal M, Groothuis D, Hirsch A (2015)

DOI: 10.1039/C5MD00157A

Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

Hartman A, Mondal M, Radeva N, Klebe G, Hirsch A (2015)

International journal of molecular sciences 16 (8): 19184-94DOI: 10.3390/ijms160819184

Supramolecular chemistry … and beyond

Hirsch A (2015)

Angewandte Chemie (International ed. in English) 54 (38): 11013-4DOI: 10.1002/anie.201506536

Validation of a homology model of Mycobacterium tuberculosis DXS: rationalization of observed activities of thiamine derivatives as potent inhibitors of two orthologues of DXS

Masini T, Lacy B, Monjas L, Hawksley D, Voogd A, Illarionov B, Iqbal A, Leeper F, Fischer M, Kontoyianni M, Hirsch A (2015)

Organic & biomolecular chemistry 13 (46): 11263-77DOI: 10.1039/c5ob01666e

Novel PqsR Inverse Agonists

Hamed M (2015)

Patent (EP 201523196)


Development of inhibitors of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway enzymes as potential anti-infective agents

Masini T, Hirsch A (2014)

Journal of medicinal chemistry 57 (23): 9740-63DOI: 10.1021/jm5010978

Theoretical and structural analysis of long C-C bonds in the adducts of polycyanoethylene and anthracene derivatives and their connection to the reversibility of Diels-Alder reactions

Hirsch A, Reutenauer P, Le Moignan M, Ulrich S, Boul P, Harrowfield J, Jarowski P, Lehn J (2014)

Chemistry (Weinheim an der Bergstrasse, Germany) 20 (4): 1073-80DOI: 10.1002/chem.201303276

Structure-based design of inhibitors of the aspartic protease endothiapepsin by exploiting dynamic combinatorial chemistry

Mondal M, Radeva N, Köster H, Park A, Potamitis C, Zervou M, Klebe G, Hirsch A (2014)

Angewandte Chemie (International ed. in English) 53 (12): 3259-63DOI: 10.1002/anie.201309682

A natural-product switch for a dynamic protein interface

Scheepstra M, Nieto L, Hirsch A, Fuchs S, Leysen S, Lam C, het Panhuis L, van Boeckel C, Wienk H, Boelens R, …, Milroy L, Brunsveld L (2014)

Angewandte Chemie (International ed. in English) 53 (25): 6443-8DOI: 10.1002/anie.201403773

A doubly hermaphroditic chiral crown ether

Hirsch A, Sirlin C, Harrowfield J, Lehn J (2014)

DOI: 10.1039/C4CE00879K

De novo fragment-based design of inhibitors of DXS guided by spin-diffusion-based NMR spectroscopy

Masini T, Pilger J, Kroezen B, Illarionov B, Lottmann P, Fischer M, Griesinger C, Hirsch A (2014)

Chem. Sci. 5 (9): 3543-3551DOI: 10.1039/C4SC00588K


Druggability of the enzymes of the non-mevalonate-pathway

Masini T, Kroezen B, Hirsch A (2013)

Drug Discovery Today 18 (23-24): 1256-62DOI: 10.1016/j.drudis.2013.07.003

Total synthesis, stereochemical elucidation and biological evaluation of Ac 2 SGL; a 1,3-methyl branched sulfoglycolipid from Mycobacterium tuberculosis

Geerdink D, Horst B, Lepore M, Mori L, Puzo G, Hirsch A, Gilleron M, Libero G, Minnaard A (2013)

DOI: 10.1039/C2SC21620E

Imidazole- and Benzimidazole-Based Inhibitors of the Kinase IspE: Targeting the Substrate-Binding Site and the Triphosphate-Binding Loop of the ATP Site

Mombelli P, Le Chapelain C, Munzinger N, Joliat E, Illarionov B, Schweizer W, Hirsch A, Fischer M, Bacher A, Diederich F (2013)

DOI: 10.1002/EJOC.201201467

Exploiting specific interactions toward next-generation polymeric drug transporters

Wieczorek S, Krause E, Hackbarth S, Röder B, Hirsch A, Börner H (2013)

Journal of the American Chemical Society 135 (5): 1711-4DOI: 10.1021/ja311895z


Total synthesis of (-)-doliculide, structure-activity relationship studies and its binding to F-actin

Matcha K, Madduri A, Roy S, Ziegler S, Waldmann H, Hirsch A, Minnaard A (2012)

ChemBioChem 13 (17): 2537-48DOI: 10.1002/cbic.201200512

The isoprenoid-precursor dependence of Plasmodium spp

van der Meer J, Hirsch A (2012)

Natural product reports 29 (7): 721-8DOI: 10.1039/c2np20013a

Metal-ion-induced shape switching: Stereoselective formation of a dinuclear Hg(II) double helicate from a hydrazonobis(acylhydrazone) ligand

Schaeffer G, Harrowfield J, Lehn J, Hirsch A (2012)

DOI: 10.1016/J.POLY.2012.04.013

Biodynamers: self-organization-driven formation of doubly dynamic proteoids

Hirsch A, Buhler E, Lehn J (2012)

Journal of the American Chemical Society 134 (9): 4177-83DOI: 10.1021/ja2099134

Exploring the Ribose Sub-Pocket of the Substrate-Binding Site in Escherichia coli IspE: Structure-Based Design, Synthesis, and Biological Evaluation of Cytosines and Cytosine Analogues

Schütz A, Osawa S, Mathis J, Hirsch A, Bernet B, Illarionov B, Fischer M, Bacher A, Diederich F (2012)

DOI: 10.1002/EJOC.201200296


Bioconjugates to specifically render inhibitors water-soluble

Hirsch A, Diederich F, Antonietti M, Börner H (2009)

Soft Matter 6 (1): 88-91DOI: 10.1039/B915928B


The Non-Mevalonate Pathway to Isoprenoid Biosynthesis: A Potential Source of New Drug Targets

Hirsch A, Diederich F (2008)

CHIMIA 62 (4): 226-230DOI: 10.2533/chimia.2008.226

Synthesis and characterization of cytidine derivatives that inhibit the kinase IspE of the non-mevalonate pathway for isoprenoid biosynthesis

Crane C, Hirsch A, Alphey M, Sgraja T, Lauw S, Illarionova V, Rohdich F, Eisenreich W, Hunter W, Bacher A, Diederich F (2008)

ChemMedChem 3 (1): 91-101DOI: 10.1002/cmdc.200700208

Inhibitors of the kinase IspE: structure-activity relationships and co-crystal structure analysis

Hirsch A, Alphey M, Lauw S, Seet M, Barandun L, Eisenreich W, Rohdich F, Hunter W, Bacher A, Diederich F (2008)

Organic & biomolecular chemistry 6 (15): 2719-30DOI: 10.1039/b804375b


Phosphate recognition in structural biology

Hirsch A, Fischer F, Diederich F (2007)

Angewandte Chemie (International ed. in English) 46 (3): 338-52DOI: 10.1002/anie.200603420

Nonphosphate inhibitors of IspE protein, a kinase in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antimalarial therapy

Hirsch A, Lauw S, Gersbach P, Schweizer W, Rohdich F, Eisenreich W, Bacher A, Diederich F (2007)

ChemMedChem 2 (6): 806-10DOI: 10.1002/cmdc.200700014


Double conjugate addition of dithiols to propargylic carbonyl systems to generate protected 1,3-dicarbonyl compounds

Sneddon H, van den Heuvel A, Hirsch A, Booth R, Shaw D, Gaunt M, Ley S (2006)

The Journal of organic chemistry 71 (7): 2715-25DOI: 10.1021/jo052514s