Publications

2024

• Xia, Q.; Fu, Q.; Shen, C.; Brenk, R.; Huang, N. Assessing Small Molecule Conformational Sampling Methods in Molecular Docking. Journal of Computational Chemistry. [DOI].

• Fahimeh Khorsand; Bengt  Erik Haug; Inari Kursula; Nathalie Reuter; Ruth Brenk. Expression and Purification of Human Neutrophil Proteinase 3 from Insect Cells and Characterization of Ligand Binding. PLoS ONE 2024, 19(6): e0294827. [DOI|bioRxiv].

• Brenk, R.; Wu, P.; Duca, M. Introduction to the Themed Collection on ‘Targeting RNA with Small Molecules.’ RSC Med. Chem. 2024. [DOI]

• Schuck, B.; Brenk, R. On the Hunt for Metalloenzyme Inhibitors: Investigating the Presence of Metal-Coordinating Compounds in Screening Libraries and Chemical Spaces. Archiv der Pharmazie, 2024, e2300648. [Pubmed|DOI|ChemRvix]

• Gartan, P.; Khorsand, F.; Mizar, P.; Vahokovski, J. I.; Cervantes, L. F.; Haug, B. E.; Brenk, R.; Brooks, C. L. I.; Reuter, N. Investigating Polypharmacology through Targeting Known Human Neutrophil Elastase Inhibitors to Proteinase 3. J. Chem. Inf. Model. 2024. [Pubmed|DOI]

• Jalencas, X.; Berg, H.; Espeland, L. O.; Sreeramulu, S.; Kinnen, F.; Richter, C.; Georgiou, C.; Yadrykhinsky, V.; Specker, E.; Jaudzems, K.; Miletić, T.; Harmel, R.; Gribbon, P.; Schwalbe, H.; Brenk, R.; Jirgensons, A.; Zaliani, A.; Mestres, J. Design, Quality and Validation of the EU-OPENSCREEN Fragment Library Poised to a High-Throughput Screening Collection. RSC Med. Chem. 2024. [DOI|PractialFragments].

2023

• Patil SS, Panchal V, Røstbø T,  Romanyuk S , Hollås H, Brenk R, Grindheim, AK , Vedeler A. RNA-binding is an ancient trait of the Annexin family. Front Cell Dev Biol. 2023, 15;11. [Pubmed]|[DOI] 

• Georgiou C, Espeland LO, Bukya H,Yadrykhinsky V, Haug BE, Mainkar P, Brenk R. New Starting Points for Antibiotics Targeting P. aeruginosa FabF Discovered by Crystallographic Fragment Screening Followed by Hit Expansion. ChemRxiv 2023. [DOI].

2022

• Yadrykhins'ky V, Georgiou G, Brenk R. Crystal structure of Pseudomonas aeruginosa FabB C161A, a template for structure-based design for new antibiotics [version 2; peer review 2: approved]. F1000Research. 2022, 10(Chem Inf Sci):1102. [DOI]

• Bothe S, Hänzelmann P, Böhler S, Kehrein J, Zehe M, Wiedemann C, Hellmich UA, Brenk R, Schindelin H, Sotriffer C. Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97. Commun Chem.  2022, 5, 169. [DOI]

2021

• Panchal V, Brenk R. Riboswitches as Drug Targets for Antibiotics. Antibiotics. 2021; 10(1):45.[DOI] (Highlighted as Editor's choice article)
• Espeland LO,  Georgiou C, Klein R, Bhukya H, Haug BE, Underhaug J, Mainkar PS, Brenk R. An Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics. ChemMedChem. 2021. [Pubmed]|[DOI]|[ChemRxiv]
• Rekand IH, Brenk R.  DrugPred_RNA-A Tool for Structure-Based Druggability Predictions for RNA Binding Sites. J Chem Inf Model 2021.[Pubmed]|[DOI]|[ChemRxiv]
• Lundquist KP, Panchal V, Gotfredsen CH, Brenk R, Clausen  MH. Fragment-Based Drug Discovery for RNA Targets. ChemMedChem. 2021. [Pubmed]|[DOI]

2020

• Klein R, Cendron L, Montanari M, Bellio P, Celenza G, Maso L, Tondi D, Brenk R. Targeting the Class A Carbapenemase GES-5 via Virtual Screening. Biomolecules. 2020 Feb 14;10(2). pii: E304.[Pubmed | DOI]
• Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R. How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System. J Med Chem. 2020 Mar 12;63(5):2095-2113 [Pubmed | DOI]

2019

• Irsheid L, Wehler T, Borek C, Kiefer W, Brenk R, Ortiz-Soto ME, Seibel J, Schirmeister T. Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design. PLoS One. 2019 May 8;14(5):e0216132. [Pubmed | DOI]urlurl

2018

• Klein R, Linciano P, Celenza G, Bellio P, Papaioannou S, Blazquez J, Cendron L, Brenk R, Tondi D. In silico identification and experimental validation of hits active against KPC-2 β-lactamase. PLoS One. 2018 Nov 29;13(11):e0203241. [Pubmed | DOI | bioRxiv]
• Harrison JR, Brand S, Smith V, Robinson DA, Thompson S, Smith A, Davies K, Mok N, Torrie LS, Collie I, Hallyburton I, Norval S, Simeons FRC, Stojanovski L, Frearson JA, Brenk R, Wyatt PG, Gilbert IH, Read KD. A Molecular Hybridization Approach for the Design of Potent, Highly Selective, and Brain-Penetrant N-Myristoyltransferase Inhibitors. J Med Chem (2018), Sep 27;61(18):8374-8389. [Pubmed | DOI]

2017

• Bayliss T, Robinson DA, Smith VC, Brand S, McElroy SP, Torrie LS, Mpamhanga C, Norval S, Stojanovski L, Brenk R, Frearson JA, Read KD, Gilbert IH, Wyatt PG. Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors. J Med Chem (2017), Dec 14;60(23):9790-9806. [Pubmed | DOI]

• Rekand IH, Brenk R. Ligand design for riboswitches, an emerging target class for novel antibiotics. Future Med Chem. 2017 Sep;9(14):1649-1662. [Pubmed | DOI | Post-Print-Version]

• Wehler, T.; Brenk, R. Structure-Based Discovery of Small Molecules Binding to RNA. In RNA Therapeutics; Topics in Medicinal Chemistry; Springer, 2017; pp 47–77. [DOI]

2015

• Baum B, Lecker LS, Zoltner M, Jaenicke E, Schnell R, Hunter WN, Brenk R. Structures of Pseudomonas aeruginosa beta-ketoacyl-(acyl-carrier-protein) synthase II (FabF) and a C164Q mutant provide templates for antibacterial drug discovery and identify a buried potassium ion and a ligand-binding site that is an artefact of the cry. Acta Crystallogr F Struct Biol Commun 71 (Pt 8), 1020-6 (2015). [Pubmed | DOI]

• Saeed ME, Kadioglu O, Seo EJ, Greten HJ, Brenk R, Efferth T. Quantitative structure-activity relationship and molecular docking of artemisinin derivatives to vascular endothelial growth factor receptor 1. Anticancer Res 35 (4), 1929-34 (2015). [Pubmed | DOI]

• Sarkar A, Brenk R. To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins. PLoS One 10 (9), e0137279 (2015). [Pubmed | DOI]

• Spinks D, Smith V, Thompson S, Robinson DA, Luksch T, Smith A, Torrie LS, McElroy S, Stojanovski L, Norval S, Collie IT, Hallyburton I, Rao B, Brand S, Brenk R, Frearson JA, Read KD, Wyatt PG, Gilbert IH. Development of Small-Molecule Trypanosoma brucei N-Myristoyltransferase Inhibitors: Discovery and Optimisation of a Novel Binding Mode. ChemMedChem 10 (11), 1821-36 (2015). [Pubmed | DOI]

• Zeino M, Brenk R, Gruber L, Zehl M, Urban E, Kopp B, Efferth T. Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na/K-ATPase. J Steroid Biochem Mol Biol 150, 97-111 (2015). [Pubmed | DOI]

2014

41. Brand S, Norcross NR, Thompson S, Harrison JR, Smith VC, Robinson DA, Torrie LS, McElroy SP, Hallyburton I, Norval S, Scullion P, Stojanovski L, Simeons FR, van Aalten D, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Wyatt PG, Gilbert IH, Read KD. Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma brucei N-Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis. J Med Chem 57 (23), 9855-69 (2014). [Pubmed | DOI | F1000 recommended]

40. Daldrop P, Brenk R. Structure-Based Virtual Screening for the Identification of RNA-Binding Ligands. Methods Mol Biol 1103, 127-39 (2014). [Pubmed | DOI]

39. Mok NY, Brenk R, Brown N. Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening. J Chem Inf Model 54 (1), 79-85 (2014). [Pubmed | DOI | F1000 recommended | practicalfragments.blogspot.co.uk]

38. Urich R, Grimaldi R, Luksch T, Frearson JA, Brenk R, Wyatt PG. The design and synthesis of potent and selective inhibitors of Trypanosoma brucei glycogen synthase kinase 3 for the treatment of human african trypanosomiasis. J Med Chem 57 (18), 7536-49 (2014). [Pubmed | DOI]

2013

37. Alphey MS, Pirrie L, Torrie LS, Boulkeroua WA, Gardiner M, Sarkar A, Maringer M, Oehlmann W, Brenk R, Scherman MS, McNeil M, Rejzek M, Field RA, Singh M, Gray D, Westwood NJ, Naismith JH. Allosteric competitive inhibitors of the glucose-1-phosphate thymidylyltransferase (RmlA) from Pseudomonas aeruginosa. ACS Chem Biol 8 (2), 387-96 (2013). [Pubmed | DOI]

36. Mok NY, Maxe S, Brenk R. Locating Sweet Spots for Screening Hits and Evaluating Pan-Assay Interference Filters from the Performance Analysis of Two Lead-like Libraries. J Chem Inf Model 53 (3), 534–44 (2013). [Pubmed | DOI]

35. Moynie L, Leckie SM, McMahon SA, Duthie FG, Koehnke A, Taylor JW, Alphey MS, Brenk R, Smith AD, Naismith JH. Structural insights into the mechanism and inhibition of the beta-hydroxydecanoyl-acyl carrier protein dehydratase from Pseudomonas aeruginosa. J Mol Biol 425 (2), 365-77 (2013). [Pubmed | DOI]

34. Urich R, Wishart G, Kiczun M, Richters A, Tidten-Luksch N, Rauh D, Sherborne B, Wyatt PG, Brenk R. De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments. ACS Chem Biol 8 (5), 1044-52 (2013). [Pubmed | DOI]

33. Woodland A, Grimaldi R, Luksch T, Cleghorn LA, Ojo KK, Van Voorhis WC, Brenk R, Frearson JA, Gilbert IH, Wyatt PG. From On-Target to Off-Target Activity: Identification and Optimisation of Trypanosoma brucei GSK3 Inhibitors and Their Characterisation as Anti-Trypanosoma brucei Drug Discovery Lead Molecules. ChemMedChem 8 (7), 1127-37 (2013). [Pubmed | DOI]

2012

32. Brand S, Cleghorn LA, McElroy SP, Robinson DA, Smith VC, Hallyburton I, Harrison JR, Norcross NR, Spinks D, Bayliss T, Norval S, Stojanovski L, Torrie LS, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Read KD, Wyatt PG, Gilbert IH. Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. J Med Chem 55 (1), 88 (2012). [Pubmed | DOI]

31. Brenk R, Rauh D. Change or be changed: Reflections of the workshop 'Future in Medicinal Chemistry'. Bioorg Med Chem 20 (12), 3695-7 (2012). [Pubmed | DOI]

30. Tidten-Luksch N, Grimaldi R, Torrie LS, Frearson JA, Hunter WN, Brenk R. IspE Inhibitors Identified by a Combination of In Silico and In Vitro High-Throughput Screening. PLoS One 7 (4), e35792 (2012). [Pubmed | DOI]

2011

29. Cappel D, Wahlstrom R, Brenk R, Sotriffer CA. Probing the Dynamic Nature of Water Molecules and Their Influences on Ligand Binding in a Model Binding Site. J Chem Inf Model 51 (10), 2581-94 (2011). [Pubmed | DOI | PDB 2Y5A]

28. Cleghorn LA, Woodland A, Collie IT, Torrie LS, Norcross N, Luksch T, Mpamhanga C, Walker RG, Mottram JC, Brenk R, Frearson JA, Gilbert IH, Wyatt PG. Identification of Inhibitors of the Leishmania cdc-Related Protein Kinase CRK3. ChemMedChem , (2011). [Pubmed | DOI]

27. Daldrop P, Reyes FE, Robinson DA, Hammond CM, Lilley DM, Batey RT, Brenk R. Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking. Chem Biol 18 (3), 324-35 (2011). [Pubmed | DOI]

26. Krasowski A, Muthas D, Sarkar A, Schmitt S, Brenk R. DrugPred: A Structure-Based Approach To Predict Protein Druggability Developed Using an Extensive Nonredundant Data Set. J Chem Inf Model 51 (11), 2829-42 (2011). [Pubmed | DOI]

25. Mok NY, Brenk R. Mining the ChEMBL Database: An Efficient Chemoinformatics Workflow for Assembling an Ion Channel-Focused Screening Library. J Chem Inf Model 51 (10), 2449-54 (2011). [Pubmed | DOI]

24. Smith VC, Cleghorn LA, Woodland A, Spinks D, Hallyburton I, Collie IT, Yi Mok N, Norval S, Brenk R, Fairlamb AH, Frearson JA, Read KD, Gilbert IH, Wyatt PG. Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488. ChemMedChem 6 (10), 1832-40 (2011). [Pubmed | DOI]

23. Spinks D, Ong HB, Mpamhanga CP, Shanks EJ, Robinson DA, Collie IT, Read KD, Frearson JA, Wyatt PG, Brenk R, Fairlamb AH, Gilbert IH. Design, Synthesis and Biological Evaluation of Novel Inhibitors of Trypanosoma brucei Pteridine Reductase 1. ChemMedChem 6 (2), 302-8 (2011). [Pubmed | DOI]

2010

22. Bhat VT, Caniard AM, Luksch T, Brenk R, Campopiano DJ, Greaney MF. Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry. Nat Chem 2 (6), 490-7 (2010). [Pubmed | DOI]

21. Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature 464 (7289), 728-32 (2010). [Pubmed | DOI | F1000 recommended]

20. Ruda GF, Campbell G, Alibu VP, Barrett MP, Brenk R, Gilbert IH. Virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase. Bioorg Med Chem 18 (14), 5056-62 (2010). [Pubmed | DOI]

2009

19. Engeholm M, de Jager M, Flaus A, Brenk R, van Noort J, Owen-Hughes T. Nucleosomes can invade DNA territories occupied by their neighbors. Nat Struct Mol Biol 16 (2), 151-8 (2009). [Pubmed | DOI | F1000 recommended]

18. Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R. One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening. J Med Chem 52 (14), 4454-65 (2009). [Pubmed | DOI | F1000 recommended | Practical Fragments]

17. Ramsden NL, Buetow L, Dawson A, Kemp LA, Ulaganathan V, Brenk R, Klebe G, Hunter WN. A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy. J Med Chem 52 (8), 2531-42 (2009). [Pubmed | DOI]

2008

16. Brenk R, Schipani A, James D, Krasowski A, Gilbert IH, Frearson J, Wyatt PG. Lessons Learnt from Assembling Screening Libraries for Drug Discovery for Neglected Diseases. ChemMedChem 3 (3), 435-444 (2008). [Pubmed | DOI]

15. Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, Rayment I, Westwood NJ. The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design. Org Biomol Chem 6 (12), 2076-84 (2008). [Pubmed | DOI | Hot paper]

2007

14. Stengl B, Meyer EA, Heine A, Brenk R, Diederich F, Klebe G. Crystal structures of tRNA-guanine transglycosylase (TGT) in complex with novel and potent inhibitors unravel pronounced induced-fit adaptations and suggest dimer formation upon substrate binding. J Mol Biol 370 (3), 492-511 (2007). [Pubmed | DOI | PDB 2BBF | PDB 1Y5V | PDB 1Y5X | PDB 1Y5W]

      2006

13. Brenk R, Klebe G. "Hot Spot" Analysis of Protein-binding Sites as a Prerequisite for Structure-based Virtual Screening and Lead Optimization. In Pharmacophores and Pharmacophore Searches (ed. Langer T, Hoffmann RD), pp. (Wiley, Weinheim, 2006). [Wiley]

12. Brenk R, Vetter SW, Boyce SE, Goodin DB, Shoichet BK. Probing molecular docking in a charged model binding site. J Mol Biol 357 (5), 1449-70 (2006). [Pubmed | DOI]

11. Meyer EA, Donati N, Guillot M, Schweizer WB, Diederich F, Stengl B, Brenk R, Renter K, Klebe G. Synthesis, biological evaluation, and crystallographic studies of extended guanine-based (lin-benzoguanine) inhibitors for tRNA-Guanine transglycosylase (TGT). Helvetica Chimica Acta 89 (4), 573-97 (2006). [DOI]

10. Peifer C, Stoiber T, Unger E, Totzke F, Schachtele C, Marme D, Brenk R, Klebe G, Schollmeyer D, Dannhardt G. Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem 49 (4), 1271-81 (2006). [Pubmed | DOI]

9. Urbaniak MD, Tabudravu JN, Msaki A, Matera KM, Brenk R, Jaspars M, Ferguson MA. Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness. Bioorg Med Chem Lett 16 (22), 5744-7 (2006). [Pubmed | DOI]

2005

8. Brenk R, Irwin JJ, Shoichet BK. Here be dragons: docking and screening in an uncharted region of chemical space. J Biomol Screen 10 (7), 667-74 (2005). [Pubmed | DOI]

7. Graves AP, Brenk R, Shoichet BK. Decoys for Docking. J Med Chem 48 (11), 3714 - 372 (2005). [Pubmed | DOI | PDB 1XEP | F1000 recommended]

2004

6. Brenk R, Meyer E, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G. Crystallographic Study of Inhibitors of tRNA-guanine Transglycosylase Suggests a New Structure-based Pharmacophore for Virtual Screening. J Mol Biol 338 (1), 55-75 (2004). [Pubmed | DOI | PDB 1Q4W | PDB 1R5Y | PDB 1Q63 | PDB 1Q65 | PDB 1Q66]

5. Meyer EA, Furler M, Diederich F, Brenk R, Klebe G. Synthesis and In Vitro Evaluation of 2-Aminoquinazolin-4(3H)-one-Based Inhibitors for tRNA-Guanine Transglycosylase (TGT). Helvetica Chimica Acta 87 (6), 1333-1356 (2004). [DOI | PDB 1S38 | PDB 1S39]

2003

4. Brenk R, Naerum L, Graedler U, Gerber HD, Garcia GA, Reuter K, Stubbs MT, Klebe G. Virtual Screening for Submicromolar Leads of tRNA-guanine Transglycosylase Based on a New Unexpected Binding Mode Detected by Crystal Structure Analysis. J Med Chem 6 (7), 1133-43 (2003). [Pubmed | DOI | PDB 1N2V]

3. Brenk R, Gerber HD, Kittendorf JD, Garcia GA, Reuter K, Klebe G. From Hit to Lead: De Novo Design Based on Virtual Screening Hits of Inhibitors of tRNA-Guanine Transglycosylase, a Putative Target of Shigellosis Therapy. Helvetica Chimica Acta 86 (5), 1435-52 (2003). [DOI]

2. Brenk R, Stubbs MT, Heine A, Reuter K, Klebe G. Flexible Adaptations in the Structure of the tRNA-Modifying Enzyme tRNA-Guanine Transglycosylase and Their Implications for Substrate Selectivity, Reaction Mechanism and Structure- Based Drug Design. Chembiochem 4 (10), 1066-77 (2003). [Pubmed | DOI | PDB 1OZM | PDB 1OZQ | PDB 1P0B | PDB 1P0D | PDB 1P0E]

2002

1. Meyer EA, Brenk R, Castellano RK, Furler M, Klebe G, Diederich, F. De novo design, synthesis, and in vitro evaluation of inhibitors for prokaryotic tRNA-guanine transglycosylase: a dramatic sulfur effect on binding affinity. Chembiochem 3 (2-3), 250-3 (2002). [Pubmed | DOI | PDB 1K4G | PDB 1K4H]