Check the updated list of publications.
2024
67. Expression and purification of human neutrophil proteinase 3 from insect cells and characterization of ligand binding.
Khorsand F, Haug BE, Kursula I, Reuter N, Brenk R. PLoS One. 2024 19(6): e0294827. 10.1371/journal.pone.0294827
66. Introduction to the themed collection on ‘targeting RNA with small molecules’.
Brenk R, Wu P, Duca M. RSC Med Chem. 2024. 10.1039/d4md90017k
65. On the hunt for metalloenzyme inhibitors: investigating the presence of metal-coordinating compounds in screening libraries and chemical spaces.
Schuck B, Brenk R. Archiv der Pharmazie. 2024 e2300648. 10.1002/ardp.202300648
64. Investigating polypharmacology through targeting known human neutrophil elastase Inhibitors to proteinase 3.
Gartan P, Khorsand F, Mizar P, Vahokovski JI, Cervantes LF, Haug BE, Brenk R, Brooks CLI, Reuter N. J. Chem Inf Model. 2024. 10.1021/acs.jcim.3c01949
63. Design, quality and validation of the EU-OPENSCREEN fragment library poised to a high-throughput screening collection.
Jalencas X, Berg H, Espeland LO, 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. RSC Med Chem. 2024. 10.1039/d3md00724c
2023
62. RNA-binding is an ancient trait of the Annexin family.
Patil SS, Panchal V, Røstbø T, Romanyuk S, Hollås H, Brenk R, Grindheim AK, Vedeler A. Front Cell Dev Biol. 2023 15;11. 10.3389/fcell.2023.1161588
61. New starting points for antibiotics targeting P. aeruginosa FabF discovered by crystallographic fragment screening followed by hit expansion.
Georgiou C, Espeland LO, Bukya H, Yadrykhinsky V, Haug BE, Mainkar P, Brenk R. ChemRxiv. 2023. 10.26434/chemrxiv-2023-cwk25
2022
60. Crystal structure of Pseudomonas aeruginosa FabB C161A, a template for structure-based design for new antibiotics [version 2; peer review 2: approved].
Yadrykhins’ky V, Georgiou G, Brenk R. F1000Research. 2022 10(Chem Inf Sci):1102. 10.12688/f1000research.74018.2
59. Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97.
Bothe S, Hänzelmann P, Böhler S, Kehrein J, Zehe M, Wiedemann C, Hellmich UA, Brenk R, Schindelin H, Sotriffer C. Commun Chem. 2022 5, 169. 10.1038/s42004-022-00782-5
2021
58. Riboswitches as drug targets for antibiotics.
Panchal V, Brenk R. Antibiotics. 2021 10(1):45. 10.3390/antibiotics10010045
Highlighted as Editor’s choice article
57. An experimental toolbox for structure-based hit discovery for P. aeruginosa FabF, a promising target for antibiotics.
Espeland LO, Georgiou C, Klein R, Bhukya H, Haug BE, Underhaug J, Mainkar PS, Brenk R. ChemMedChem. 2021. 10.1002/cmdc.202100302
56. DrugPred_RNA-A tool for structure-based druggability predictions for RNA binding sites.
Rekand IH, Brenk R. J Chem Inf Model. 2021. 10.1021/acs.jcim.1c00155
55. Fragment-based drug discovery for RNA targets.
Lundquist KP, Panchal V, Gotfredsen CH, Brenk R, Clausen MH. ChemMedChem. 2021. 10.1002/cmdc.202100324
2020
54. Targeting the class A carbapenemase GES-5 via virtual screening.
Klein R, Cendron L, Montanari M, Bellio P, Celenza G, Maso L, Tondi D, Brenk R. Biomolecules. 2020 Feb 14;10(2) pii: E304. 10.3390/biom10020304
53. How to design selective ligands for highly conserved binding sites: a case study using N-Myristoyltransferases as a model system.
Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R. J Med Chem. 2020 Mar 12;63(5):2095-2113. 10.1021/acs.jmedchem.9b00586
2019
52. Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
Irsheid L, Wehler T, Borek C, Kiefer W, Brenk R, Ortiz-Soto ME, Seibel J, Schirmeister T. PLoS One. 2019 May 8;14(5):e0216132. 10.1371/journal.pone.0216132
2018
51. In silico identification and experimental validation of hits active against KPC-2 β-lactamase.
Klein R, Linciano P, Celenza G, Bellio P, Papaioannou S, Blazquez J, Cendron L, Brenk R, Tondi D. PLoS One. 2018 Nov 29;13(11):e0203241. 10.1371/journal.pone.0203241
50. A molecular hybridization approach for the design of potent, highly selective, and brain-penetrant N-Myristoyltransferase inhibitors.
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. J Med Chem. 2018 Sep 27;61(18):8374-8389. 10.1021/acs.jmedchem.8b00884
2017
49. Design and synthesis of brain penetrant trypanocidal N-Myristoyltransferase inhibitors.
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. J Med Chem. 2017 Dec 14;60(23):9790-9806. 10.1021/acs.jmedchem.7b01255
48. Ligand design for riboswitches, an emerging target class for novel antibiotics.
Rekand IH, Brenk R. Future Med Chem. 2017 Sep;9(14):1649-1662. 10.4155/fmc-2017-0063
47. Structure-based discovery of small molecules binding to RNA.
Wehler T, Brenk R. In RNA Therapeutics; Topics in Medicinal Chemistry; Springer. 2017 pp 47–77. 10.1007/7355_2016_29
2015
46. 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.
Baum B, Lecker LS, Zoltner M, Jaenicke E, Schnell R, Hunter WN, Brenk R. Acta Crystallogr F Struct Biol Commun. 2015 71 (Pt 8), 1020-6. 10.1107/S2053230X15010614
45. Quantitative structure-activity relationship and molecular docking of artemisinin derivatives to vascular endothelial growth factor receptor 1.
Saeed ME, Kadioglu O, Seo EJ, Greten HJ, Brenk R, Efferth T. Anticancer Res. 2015 35 (4), 1929-34. pubmed.ncbi.nlm.nih.gov/25862844/
44. To hit or not to hit, that is the question – Genome-wide structure-based druggability predictions for Pseudomonas aeruginosa proteins.
Sarkar A, Brenk R. PLoS One. 2015 10 (9), e0137279 (2015). 10.1371/journal.pone.0137279
43. Development of small-molecule Trypanosoma brucei N-myristoyltransferase inhibitors: discovery and optimisation of a novel binding mode.
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. ChemMedChem. 2015 10 (11), 1821-36. 10.1002/cmdc.201500301
42. Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na/K-ATPase.
Zeino M, Brenk R, Gruber L, Zehl M, Urban E, Kopp B, Efferth T. J Steroid Biochem Mol Biol. 2015 150, 97-111. 10.1016/j.jsbmb.2015.03.008
2014
41. 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.
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. J Med Chem. 2014 57 (23), 9855-69. 10.1021/jm500809c
40. Structure-based virtual screening for the identification of RNA-binding ligands.
Daldrop P, Brenk R. Methods Mol Biol. 2014 1103, 127-39. 10.1007/978-1-62703-730-3_10
39. Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening.
Mok NY, Brenk R, Brown N. J Chem Inf Model. 2014 54 (1), 79-85. 10.1021/ci400632y
38. The design and synthesis of potent and selective inhibitors of Trypanosoma brucei glycogen synthase kinase 3 for the treatment of human African trypanosomiasis.
Urich R, Grimaldi R, Luksch T, Frearson JA, Brenk R, Wyatt PG. J Med Chem. 2014 57 (18), 7536-49. 10.1021/jm500239b
2013
37. Allosteric competitive inhibitors of the glucose-1-phosphate thymidylyltransferase (RmlA) from Pseudomonas aeruginosa.
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. ACS Chem Biol. 2013 8 (2), 387-96. 10.1021/cb300426u
36. Locating sweet spots for screening hits and evaluating pan-assay interference filters from the performance analysis of two lead-like libraries.
Mok NY, Maxe S, Brenk R. J Chem Inf Model. 2013 53 (3), 534–44. 10.1021/ci300382f
35. Structural insights into the mechanism and inhibition of the beta-hydroxydecanoyl-acyl carrier protein dehydratase from Pseudomonas aeruginosa.
Moynie L, Leckie SM, McMahon SA, Duthie FG, Koehnke A, Taylor JW, Alphey MS, Brenk R, Smith AD, Naismith JH. J Mol Biol. 2013 425 (2), 365-77. 10.1016/j.jmb.2012.11.017
34. De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments.
Urich R, Wishart G, Kiczun M, Richters A, Tidten-Luksch N, Rauh D, Sherborne B, Wyatt PG, Brenk R. ACS Chem Biol. 2013 8 (5), 1044-52. 10.1021/cb300729y
33. 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.
Woodland A, Grimaldi R, Luksch T, Cleghorn LA, Ojo KK, Van Voorhis WC, Brenk R, Frearson JA, Gilbert IH, Wyatt PG. ChemMedChem. 2013 8 (7), 1127-37. 10.1002/cmdc.201300072
2012
32. Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.
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. J Med Chem. 2012 55 (1), 88. 10.1021/jm201091t
31. Change or be changed: Reflections of the workshop ‘Future in Medicinal Chemistry’.
Brenk R, Rauh D. Bioorg Med Chem. 2012 20 (12), 3695-7. 10.1016/j.bmc.2012.04.038
30. IspE inhibitors identified by a combination of in silico and in vitro high-throughput screening.
Tidten-Luksch N, Grimaldi R, Torrie LS, Frearson JA, Hunter WN, Brenk R. PLoS One. 2012 7 (4), e35792. 10.1371/journal.pone.0035792
2011
29. Probing the dynamic nature of water molecules and their influences on ligand binding in a model binding site.
Cappel D, Wahlstrom R, Brenk R, Sotriffer CA. J Chem Inf Model. 2011 51 (10), 2581-94. 10.1021/ci200052j
28. Identification of inhibitors of the Leishmania cdc-related protein kinase CRK3.
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. ChemMedChem. 2011. 10.1002/cmdc.201100344
27. Novel ligands for a purine riboswitch discovered by RNA-ligand docking.
Daldrop P, Reyes FE, Robinson DA, Hammond CM, Lilley DM, Batey RT, Brenk R. Chem Biol. 2011 18 (3), 324-35. 10.1016/j.chembiol.2010.12.020
26. DrugPred: A structure-based approach to predict protein druggability developed using an extensive nonredundant data set.
Krasowski A, Muthas D, Sarkar A, Schmitt S, Brenk R. J Chem Inf Model. 2011 51 (11), 2829-42. 10.1021/ci200266d
25. Mining the ChEMBL database: an efficient chemoinformatics workflow for assembling an ion channel-focused screening library.
Mok NY, Brenk R. J Chem Inf Model. 2011 51 (10), 2449-54. 10.1021/ci200260t
24. Optimisation of the anti-Trypanosoma brucei activity of the opioid agonist U50488.
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. ChemMedChem. 2011 6 (10), 1832-40. 10.1002/cmdc.201100278
23. Design, synthesis and biological evaluation of novel inhibitors of Trypanosoma brucei pteridine reductase 1.
Spinks D, Ong HB, Mpamhanga CP, Shanks EJ, Robinson DA, Collie IT, Read KD, Frearson JA, Wyatt PG, Brenk R, Fairlamb AH, Gilbert IH. ChemMedChem. 2011 6 (2), 302-8. 10.1002/cmdc.201000450
2010
22. Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry.
Bhat VT, Caniard AM, Luksch T, Brenk R, Campopiano DJ, Greaney MF. Nat Chem. 2010 2 (6), 490-7. 10.1038/nchem.658
21. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.
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. Nature. 2010 464 (7289), 728-32. 10.1038/nature08893
20. Virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase.
Ruda GF, Campbell G, Alibu VP, Barrett MP, Brenk R, Gilbert IH. Bioorg Med Chem. 2010 18 (14), 5056-62. 10.1016/j.bmc.2010.05.077
2009
19. Nucleosomes can invade DNA territories occupied by their neighbors.
Engeholm M, de Jager M, Flaus A, Brenk R, van Noort J, Owen-Hughes T. Nat Struct Mol Biol. 2009 16 (2), 151-8. 10.1038/nsmb.1551
18. One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening.
Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R. J Med Chem. 2009 52 (14), 4454-65. 10.1021/jm900414x
17. A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.
Ramsden NL, Buetow L, Dawson A, Kemp LA, Ulaganathan V, Brenk R, Klebe G, Hunter WN. J Med Chem. 2009 52 (8), 2531-42. 10.1021/jm801475n
2008
16. Lessons learnt from assembling screening libraries for drug discovery for neglected diseases.
Brenk R, Schipani A, James D, Krasowski A, Gilbert IH, Frearson J, Wyatt PG. ChemMedChem. 2008 3 (3), 435-444. 10.1002/cmdc.200700139
15. The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design.
Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, Rayment I, Westwood NJ. Org Biomol Chem. 2008 6 (12), 2076-84. 10.1039/b801223g
2007
14. 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.
Stengl B, Meyer EA, Heine A, Brenk R, Diederich F, Klebe G. J Mol Biol. 2007 370 (3), 492-511. 10.1016/j.jmb.2007.04.008
2006
13. “Hot spot” analysis of protein-binding sites as a prerequisite for structure-based virtual screening and lead optimization.
Brenk R, Klebe G. In Pharmacophores and Pharmacophore Searches (ed. Langer T, Hoffmann RD), pp. 2006 Wiley, Weinheim. 10.1002/3527609164.ch8
12. Probing molecular docking in a charged model binding site.
Brenk R, Vetter SW, Boyce SE, Goodin DB, Shoichet BK. J Mol Biol. 2006 357 (5), 1449-70. 10.1016/j.jmb.2006.01.034
11. Synthesis, biological evaluation, and crystallographic studies of extended guanine-based (lin-benzoguanine) inhibitors for tRNA-Guanine transglycosylase (TGT).
Meyer EA, Donati N, Guillot M, Schweizer WB, Diederich F, Stengl B, Brenk R, Renter K, Klebe G. Helvetica Chimica Acta. 2006 89 (4), 573-97. 10.1002/hlca.200690062
10. Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors.
Peifer C, Stoiber T, Unger E, Totzke F, Schachtele C, Marme D, Brenk R, Klebe G, Schollmeyer D, Dannhardt G. J Med Chem. 2006 49 (4), 1271-81. 10.1021/jm0580297
9. Identification of novel inhibitors of UDP-Glc 4′-epimerase, a validated drug target for African sleeping sickness.
Urbaniak MD, Tabudravu JN, Msaki A, Matera KM, Brenk R, Jaspars M, Ferguson MA. Bioorg Med Chem Lett. 2006 16 (22), 5744-7. 10.1016/j.bmcl.2006.08.091
2005
8. Here be dragons: docking and screening in an uncharted region of chemical space.
Brenk R, Irwin JJ, Shoichet BK. J Biomol Screen. 2005 10 (7), 667-74. 10.1177/1087057105281047
7. Decoys for docking.
Graves AP, Brenk R, Shoichet BK. J Med Chem. 2005 48 (11), 3714-372. 10.1021/jm0491187
2004
6. Crystallographic Study of Inhibitors of tRNA-guanine Transglycosylase Suggests a New Structure-based Pharmacophore for Virtual Screening.
Brenk R, Meyer E, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G. J Mol Biol. 2004 338 (1), 55-75. 10.1016/j.jmb.2004.02.019
5. Synthesis and in vitro evaluation of 2-aminoquinazolin-4(3H)-one-based inhibitors for tRNA-guanine transglycosylase (TGT).
Meyer EA, Furler M, Diederich F, Brenk R, Klebe G. Helvetica Chimica Acta. 2004 87 (6), 1333-1356. 10.1002/hlca.200490122
2003
4. Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis.
Brenk R, Naerum L, Graedler U, Gerber HD, Garcia GA, Reuter K, Stubbs MT, Klebe G. J Med Chem. 2003 (7), 1133-43. 10.1021/jm0209937
3. From hit to lead: de novo design based on virtual screening hits of inhibitors of tRNA-guanine transglycosylase, a putative target of shigellosis hherapy.
Brenk R, Gerber HD, Kittendorf JD, Garcia GA, Reuter K, Klebe G. Helvetica Chimica Acta. 2003 86 (5), 1435-52. 10.1002/hlca.200390128
2. 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.
Brenk R, Stubbs MT, Heine A, Reuter K, Klebe G. Chembiochem. 2003 4 (10), 1066-77. 10.1002/cbic.200300644
2002
1. De novo design, synthesis, and in vitro evaluation of inhibitors for prokaryotic tRNA-guanine transglycosylase: a dramatic sulfur effect on binding affinity.
Meyer EA, Brenk R, Castellano RK, Furler M, Klebe G, Diederich F. Chembiochem. 2002 3 (2-3), 250-3. 10.1002/1439-7633(20020301)3:2/3<250::AID-CBIC250>3.0.CO;2-J