Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery

Current Opinion in Chemical Biology

Volumn 26, Issue , 2015, Pages 62-71

  Blakskjaer, Peter ^a   Heitner, Tara ^a   Hansen, Nils Jakob Vest ^a  

^a Vipergen ApS ^*  (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

BINDER TRAP ENRICHMENT; CHEMICAL MODIFICATION; CHEMICAL REACTION; COMBINATORIAL CHEMISTRY; COMBINATORIAL LIBRARY; DNA ENCODED SMALL MOLECULE LIBRARY; DNA LIBRARY; DNA SEQUENCE; DNA STRAND; DRUG DEVELOPMENT; EMULSION; GENETIC CODE; MOLECULAR LIBRARY; NEXT GENERATION SEQUENCING; REVIEW; YOCTOREACTOR; AGONISTS; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DESIGN; GENE EXPRESSION; GENE LIBRARY; HIGH THROUGHPUT SEQUENCING; HUMAN; METABOLISM; NUCLEIC ACID AMPLIFICATION;

EMULSION; MOLECULAR LIBRARY; PROTEIN;

COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; DRUG DISCOVERY; EMULSIONS; GENE EXPRESSION; GENE LIBRARY; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; NUCLEIC ACID AMPLIFICATION TECHNIQUES; PROTEINS; SMALL MOLECULE LIBRARIES;

EID: 84923333701     PISSN: 13675931     EISSN: 18790402     Source Type: Journal    
DOI: 10.1016/j.cbpa.2015.02.003     Document Type: Review

References (53)

1. Sams-Dodd F. Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. Drug Discov Today 2013, 18:211-217.
2. Kodadek T. Rethinking screening. Nat Chem Biol 2010, 6:162-165.
3. Brenner S., Lerner R.A. Encoded combinatorial chemistry. Proc Natl Acad Sci 1992, 89:5381-5383.
4. Gartner Z.J., Tse B.N., Grubina R., Doyon J.B., Snyder T.M., Liu D.R. DNA-templated organic synthesis and selection of a library of macrocycles. Science 2004, 305:1601-1605.
5. Melkko S., Scheuermann J., Dumelin C.E., Neri D. Encoded self-assembling chemical libraries. Nat Biotechnol 2004, 5:568-574.
6. Halpin D.R., Harbury P.B. DNA display II: genetic manipulation of combinatorial chemistry libraries for small molecule evaluation. PLoS Biol 2004, 2:1022-1030.
7. Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., Smith H.O., Yandell M., Evans C.A., Holt R.A., et al. The sequence of the human genome. Science 2001, 291:1304-1351.
8. Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., et al. Initial sequencing and analysis of the human genome. Nature 2001, 409:860-921.
9. Podolin P.L., Bolognese B.J., Foley J.F., Long E., Peck B., Umbrecht S., Zhang X., Zhu P., Schwartz B., Xie W., et al. In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor. Prostaglandins Other Lipid Mediat 2013, 104:25-31.
10. Petersen L.K. Yoctoreactor DNA encoded small-molecule libraries: second generation DNA-encoded library technologies. 10th International Conference Intelligent Compound Libraries 2014.
11. Kleiner R.E., Dumelin C., Tiu G., Sakurai K., Liu D.R. In vitro selection of a DNA-templated small-molecule library reveals a class of macrocyclic kinase inhibitors. J Am Chem Soc 2010, 132:11779-11791.
12. Gilmartin A.G., Faitg T.H., Richter M., Groy A., Seefeld M.A., Darcy M.G., Peng X., Federowicz K., Yang J., Zhang S.-Y., et al. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol 2014, 10:181-187.
13. Maianiti J.P., McFedries A., Foda Z.H., Kleiner R.E., Du X.Q., Leissring M.A., Tang W.-J., Charron M.J., Seeliger M.A., Saghetelian A., Liu D.R. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature 2014, 511:94-98.
14. Georghiou G., Kleiner R.E., Pulkoski-Gross M., Liu D.R., Seeliger M.A. Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles. Nat Chem Biol 2012, 8:366-374.
15. Deng H., O'Keefe H., Davie C.P., Lind K.E., Acharya R.A., Franklin G.J., Larkin J., Matico R., Neeb M., Thompson M.M., et al. Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT). J Med Chem 2012, 55:7061-7079.
16. Encinas L., O'Keefe H., Neu M., Remuiñán M.J., Patel A.M., Guardia A., Davie C.P., Péres-Macías N., Yang H., Convery M.A., et al. Encoded library technology as a source of hits for the discovery and lead optimization of a potent and selective class of bactericidal direct inhibitors of Mycobacterium tuberculosis InhA. J Med Chem 2014, 57:1276-1288.
17. Disch J.S., Evindar G., Chiu C.H., Blum C.A., Dai H., Jin L., Schuman E., Lind Ke, Belyanskaya S.L., Deng J., et al. Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3. J Med Chem 2013, 56:3666-3679.
18. Buller F., Steiner M., Frey K., Mircsof D., Scheuermann J., Kalish M., Bühlmann P., Supuran C.T., Neri D. Selection of carbonic anhydrase IX inhibitors from one million DNA-encoded compounds. ACS Chem Biol 2011, 6:336-344.
19. Mannocci L., Melkko S., Buller F., Molnàr I., Bianké J.P.G., Dumelin C.E., Scheuermann J., Neri D. Isolation of specific trypsin inhibitors from a DNA-encoded chemical library. Bioconjug Chem 2010, 21:1836-1841.
20. Kollmann C.S., Bai X., Tsai C.-H., Yang H., Lind K.E., Skinner S.R., Zhu Z., Israel D.I., Cuozzo J.W., Morgan B.A., et al. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function associated antigen 1 (LFA-1) antagonists. Bioorg Med Chem 2014, 22:2353-2365.
21. Taylor M., Terrett N.K., Connors W.H., Shortsleeves K.C., Seigal B.A., Snedeker C., Hale S.P., Briggs T.F., Favaloro F.G., Cipriani T.J., et al. Macrocyclic Compounds for Modulating IL-17. PCT US2013/024386 2013, August.
22. Hansen N.J.V. Discovery of the first small molecule IL-17 antagonist. Protein-Protein Interaction Conference 2013.
23. Hansen N.J.V. Discovery of the first single digit nanomolar small molecule PPI blockers. 2nd Protein-Protein Interaction Conference 2014.
24. Leimbacher M., Zhang Y., Mannocci L., Stravs M., Geppert T., Scheuermann J., Schneider G., neri D. Discovery of small-molecule interleukin-2 inhibitors from DNA-encoded chemical library. Chem Eur J 2012, 18:7729-7737.
25. Arkin M.R., Tang Y., Wells J.A. Small-molecule inhibitors of protein-protein interactions: progression towards reality. Chem Biol 2014, 21:1102-1114.
26. Doran M.T., Gao Y., Mendes K., Dean S., Simanski S., Kadadek T. Utility of redundant combinatorial libraries in distinguishing high and low quality screening hits. ACS Comb Sci 2014, 16:259-270.
27. Lowe D.B. Combichem all over again. Nat Chem 2014, 6:851-852.
28. Heeres J.T., Hergenrother P.J. High-throughput screening for modulators of protein-protein interactions: uses of photonic crystal biosensors and complementary technologies. Chem Soc Rev 2011, 40:4398-4410.
29. Bleicher K.H., Böhm H.-J., Müller K., Alanine A.I. Hit and lead generation: beyond high-throughput screening. Nat Rev Drug Discov 2003, 2:369-378.
30. A Handbook for DNA-Encoded Chemistry: Theory and Applications for Exploring Chemical Space 2014, John Wiley & Sons Inc. R.A. Goodnow (Ed.).
31. Percivalle C., Bartolo J.-F., Ladame S. Oligonucleotide-templated chemical reactions: pushing the boundaries of a nature-inspired process. Org Biomol Chem 2013, 11:16-26.
32. Hann M.M., Keserü G.M. Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nat Rev Drug Discov 2012, 11:355-365.
33. Clark M.A., Acharya R.A., Arico-Muendel C.C., Belyanskaya S.L., Benjamin D.R., Carlson N.R., Centrella P.A., Chiu C.H., Creaser S.P., Cuozzo J.W., et al. Design, synthesis and selection of DNA-encoded small-molecule libraries. Nat Chem Biol 2009, 5:647-654.
34. Hansen M.H., Blakskjaer P., Petersen L.K., Hansen T.H., Hoejfeldt J.W., Gothelf K.V., Hansen N.J.V. A yoctoliter-scale DNA reactor for small molecule evolution. J Am Chem Soc 2009, 131:1322-1327.
35. Cao C., Zhao P., Li Z., Chen Z., Huang Y., Bai Y., Li X. DNA-templated synthesis of encoded small molecules by DNA self-assembly. Chem Commun 2014, 50:10997-10999.
36. Franzini R.M., Neri D., Scheuermann J. DNA encoded chemical libraries: advancing beyond conventional small-molecule libraries. Acc Chem Res 2014, 47:1247-1255.
37. Wrenn S.J., Weisinger R.M., Halpin D.R., Harbury P.B. Synthetic ligands discovered by in vitro selection. J Am Chem Soc 2007, 129:13137-13143.
38. Heitner T., Hansen N.J.V. Streamlining hit discovery and optimization with a yoctoliter scale DNA reactor. Expert Opin Drug Discov 2009, 4:1-13.
39. Gartner Z.J., Liu D.R. The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules. J Am Chem Soc 2001, 123:6961-6963.
40. Briggs-Houck J.E., Younai A., Shaw J.T. Recent advances in multicomponent reactions for diversity oriented synthesis. Curr Opin Chem Biol 2010, 14:371-382.
41. Slobbe P., Ruijter E., Orru R.V.A. Recent applications of multicomponent reactions in medicinal chemistry. Med Chem Commun 2012, 3:1189-1218.
42. Larsen L.K., Blakskjaer P., Dietvorst J., Sløk F., Christensen A.B., Petersen L.K., Holmkvist J., Heitner T.R., Hansen N.J.V. DNA-encoded chemical library technology for the discovery of small molecule inhibitors of enzyme targets and PPIs. 49th International Conference on Medicinal Chemistry - Rencontres Internationales de chemie therapeutique 2013, abstract OS09.
43. Hoejfeldt J.W., Blakskjaer P., Gothelf K.V. A cleavable amino-thiol linker for reversible linking of amines to DNA. J Org Chem 2006, 71:9556-9559.
44. McGregor L.M., Gorin D.J., Dumelin C.E., Liu D.R. Interaction-dependent PCR: identification of ligand-target pairs from libraries of ligands and libraries of targets in a single solution-phase experiment. J Am Chem Soc 2010, 132:15522-15524.
45. Zhao P., Chen Z., Li Y., Sun D., Gao Y., Huang Y., Li X. Selection of DNA-encoded small molecule libraries against unmodified and non-immobilized protein targets. Angew Chem Int Ed 2014, 53:10056-10059.
46. Hansen N.J.V., Christensen A.B., Larsen L.K., Sløk F.A., Petersen L.K., Rasmussen-Dietvorst J., Blakskjaer P., Hansen T.H., Holmkvist J. Method for Making an Enriched Library. PCT 20130288929 2013, October.
47. Stephanopoulos N., Francis M.B. Choosing and effective protein bioconjugation strategy. Nat Chem Biol 2011, 7:876-884.
48. Rosen C.B., Kodal A.L.B., Nielsen J.S., Schaffert D.H., Scavenius C., Okholm A.H., Voigt N.V., Enghild J.J., Kjems J., Toerring T., Gothelf K.V. Template-directed covalent conjugation if DNA to native antibodies, transferrin and other metal-binding proteins. Nat Chem 2014, 6:804-809.
49. Pan A.C., Borhani D.W., Dror R.O., Shaw D.E. Molecular determinants of drug-receptor binding kinetics. Drug Discov Today 2013, 18:667-673.
50. Kleiner R.E., Dumelin C.E., Liu D.R. Small-molecule discovery from DNA-encoded chemical libraries. Chem Soc Rev 2011, 40:5707-5717.
51. Clark M.A. Selecting chemicals: the emerging utility of DNA-encoded libraries. Curr Opin Chem Biol 2010, 13:1-8.
52. Nero T.L., Morton C.J., Holien J.K., Wielens J., Parker M.W. Oncogenic protein interfaces: small molecules, big challenges. Nat Rev Cancer 2014, 14:248-262.
53. Heitner T.H., Larsen L.K., Blakskjaer P., Dietvorst J., Thomas L., Sloek F., Christensen A.B., Petersen L.K., Holmkvist J., Hansen N.J.V. Efficient discovery of protein-protein interaction inhibitors using high fidelity DNA-encoded small-molecule library technologies. 4th International Symposium on DNA-Encoded Chemical Libraries 2014.