Synthesis and screening of small-molecule α-helix mimetic libraries targeting protein-protein interactions

Current Opinion in Chemical Biology

Volumn 24, Issue , 2015, Pages 38-47

  Moon, Heejo ^a   Lim, Hyun Suk ^a,b  

^a Pohang University of Science and Technology (POSTECH)   (South Korea)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA HELIX; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; PEPTIDE LIBRARY; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; PROTEIN TARGETING; REVIEW; SCREENING; SOLID PHASE SYNTHESIS; ANIMAL; BIOMIMETICS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY; PROCEDURES; PROTEIN SECONDARY STRUCTURE; SYNTHESIS;

MOLECULAR LIBRARY; PROTEIN;

ANIMALS; BIOMIMETICS; CHEMISTRY TECHNIQUES, SYNTHETIC; DRUG DISCOVERY; HUMANS; PROTEIN INTERACTION MAPS; PROTEIN STRUCTURE, SECONDARY; PROTEINS; SMALL MOLECULE LIBRARIES;

EID: 84909606557     PISSN: 13675931     EISSN: 18790402     Source Type: Journal    
DOI: 10.1016/j.cbpa.2014.10.023     Document Type: Review

References (69)

1. Arkin M.R., Wells J.A. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov 2004, 3:301-317.
2. Wells J.A., McClendon C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007, 450:1001-1009.
3. Arkin M.R., Whitty A. The road less traveled: modulating signal transduction enzymes by inhibiting their protein-protein interactions. Curr Opin Chem Biol 2009, 13:284-290.
4. Whitty A., Kumaravel G. Between a rock and a hard place?. Nat Chem Biol 2006, 2:112-118.
5. Bullock B.N., Jochim A.L., Arora P.S. Assessing helical protein interfaces for inhibitor design. J Am Chem Soc 2011, 133:14220-14223.
6. Jochim A.L., Arora P.S. Systematic analysis of helical protein interfaces reveals targets for synthetic inhibitors. ACS Chem Biol 2010, 5:919-923.
7. Henchey L.K., Jochim A.L., Arora P.S. Contemporary strategies for the stabilization of peptides in the alpha-helical conformation. Curr Opin Chem Biol 2008, 12:692-697.
8. Jayatunga M.K., Thompson S., Hamilton A.D. Alpha-helix mimetics: outwards and upwards. Bioorg Med Chem Lett 2014, 24:717-724.
9. Cummings C.G., Hamilton A.D. Disrupting protein-protein interactions with non-peptidic, small molecule alpha-helix mimetics. Curr Opin Chem Biol 2010, 14:341-346.
10. Azzarito V., Long K., Murphy N.S., Wilson A.J. Inhibition of alpha-helix-mediated protein-protein interactions using designed molecules. Nat Chem 2013, 5:161-173.
11. Rutledge S.E., Volkman H.M., Schepartz A. Molecular recognition of protein surfaces: high affinity ligands for the cbp kix domain. J Am Chem Soc 2003, 125:14336-14347.
12. Li C., Pazgier M., Liu M., Lu W.Y., Lu W. Apamin as a template for structure-based rational design of potent peptide activators of p53. Angew Chem Int Ed Engl 2009, 48:8712-8715.
13. Bernal F., Tyler A.F., Korsmeyer S.J., Walensky L.D., Verdine G.L. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J Am Chem Soc 2007, 129:5298.
14. Chapman R.N., Dimartino G., Arora P.S. A highly stable short alpha-helix constrained by a main-chain hydrogen-bond surrogate. J Am Chem Soc 2004, 126:12252-12253.
15. Horne W.S., Gellman S.H. Foldamers with heterogeneous backbones. Acc Chem Res 2008, 41:1399-1408.
16. Kritzer J.A., Lear J.D., Hodsdon M.E., Schepartz A. Helical beta-peptide inhibitors of the p53-hDM2 interaction. J Am Chem Soc 2004, 126:9468-9469.
17. Fasan R., Dias R.L., Moehle K., Zerbe O., Vrijbloed J.W., Obrecht D., Robinson J.A. Using a beta-hairpin to mimic an alpha-helix: cyclic peptidomimetic inhibitors of the p53-hDM2 protein-protein interaction. Angew Chem Int Ed Engl 2004, 43:2109-2112.
18. Wu C.W., Sanborn T.J., Zuckermann R.N., Barron A.E. Peptoid oligomers with alpha-chiral, aromatic side chains: effects of chain length on secondary structure. J Am Chem Soc 2001, 123:2958-2963.
19. Hara T., Durell S.R., Myers M.C., Appella D.H. Probing the structural requirements of peptoids that inhibit hDM2-p53 interactions. J Am Chem Soc 2006, 128:1995-2004.
20. Orner B.P., Ernst J.T., Hamilton A.D. Toward proteomimetics: terphenyl derivatives as structural and functional mimics of extended regions of an alpha-helix. J Am Chem Soc 2001, 123:5382-5383.
21. Lanning M., Fletcher S. Recapitulating the alpha-helix: nonpeptidic, low-molecular-weight ligands for the modulation of helix-mediated protein-protein interactions. Future Med Chem 2013, 5:2157-2174.
22. Ravindranathan P., Lee T.K., Yang L., Centenera M.M., Butler L., Tilley W.D., Hsieh J.T., Ahn J.M., Raj G.V. Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer. Nat Commun 2013, 4:1923.
23. Kazi A., Sun J., Doi K., Sung S.S., Takahashi Y., Yin H., Rodriguez J.M., Becerril J., Berndt N., Hamilton A.D., Wang H.G., et al. The BH3 alpha-helical mimic BH3-M6 disrupts BCL-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem 2011, 286:9382-9392.
24. Lao B.B., Grishagin I., Mesallati H., Brewer T.F., Olenyuk B.Z., Arora P.S. In vivo modulation of hypoxia-inducible signaling by topographical helix mimetics. Proc Natl Acad Sci U S A 2014, 111:7531-7536.
25. Cao X., Yap J.L., Newell-Rogers M.K., Peddaboina C., Jiang W., Papaconstantinou H.T., Jupitor D., Rai A., Jung K.Y., Tubin R.P., Yu W., et al. The novel BH3 alpha-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xl and Mcl-1 protein-protein interactions with bak. Mol Cancer 2013, 12:42.
26. Naduthambi D., Bhor S., Elbaum M.B., Zondlo N.J. Synthesis of a tetrasubstituted tetrahydronaphthalene scaffold for alpha-helix mimicry via a MgBr2-catalyzed Friedel-Crafts epoxide cycloalkylation. Org Lett 2013, 15:4892-4895.
27. Peters M., Trobe M., Breinbauer R. A modular synthesis of teraryl-based alpha-helix mimetics, part 2: synthesis of 5-pyridine boronic acid pinacol ester building blocks with amino acid side chains in 3-position. Chemistry 2013, 19:2450-2456.
28. Adler M.J., Hamilton A.D. Oligophenylenaminones as scaffolds for alpha-helix mimicry. J Org Chem 2011, 76:7040-7047.
29. Anderson L., Zhou M., Sharma V., McLaughlin J.M., Santiago D.N., Fronczek F.R., Guida W.C., McLaughlin M.L. Facile iterative synthesis of 2,5-terpyrimidinylenes as nonpeptidic alpha-helical mimics. J Org Chem 2010, 75:4288-4291.
30. Volonterio A., Moisan L., Rebek J. Synthesis of pyridazine-based scaffolds as alpha-helix mimetics. Org Lett 2007, 9:3733-3736.
31. Maity P., Konig B. Synthesis and structure of 1,4-dipiperazino benzenes: chiral terphenyl-type peptide helix mimetics. Org Lett 2008, 10:1473-1476.
32. Saraogi I., Incarvito C.D., Hamilton A.D. Controlling curvature in a family of oligoamide alpha-helix mimetics. Angew Chem Int Ed Engl 2008, 47:9691-9694.
33. Plante J.P., Burnley T., Malkova B., Webb M.E., Warriner S.L., Edwards T.A., Wilson A.J. Oligobenzamide proteomimetic inhibitors of the p53-hDM2 protein-protein interaction. Chem Commun 2009, 34:5091-5093.
34. Ernst J.T., Becerril J., Park H.S., Yin H., Hamilton A.D. Design and application of an alpha-helix-mimetic scaffold based on an oligoamide-foldamer strategy: antagonism of the Bak BH3/Bcl-xL complex. Angew Chem Int Ed Engl 2003, 42:535-539.
35. Shaginian A., Whitby L.R., Hong S., Hwang I., Farooqi B., Searcey M., Chen J., Vogt P.K., Boger D.L. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions. J Am Chem Soc 2009, 131:5564-5572.
36. Plante J.P., Burnley T., Malkova B., Webb M.E., Warriner S.L., Edwards T.A., Wilson A.J. Oligobenzamide proteomimetic inhibitors of the p53-hDM2 protein-protein interaction. Chem Commun (Camb) 2009, 34:5091-5093.
37. Murphy N.S., Prabhakaran P., Azzarito V., Plante J.P., Hardie M.J., Kilner C.A., Warriner S.L., Wilson A.J. Solid-phase methodology for synthesis of o-alkylated aromatic oligoamide inhibitors of alpha-helix-mediated protein-protein interactions. Chemistry 2013, 19:5546-5550.
38. Azzarito V., Prabhakaran P., Bartlett A.I., Murphy N.S., Hardie M.J., Kilner C.A., Edwards T.A., Warriner S.L., Wilson A.J. 2-o-alkylated para-benzamide alpha-helix mimetics: the role of scaffold curvature. Org Biomol Chem 2012, 10:6469-6472.
39. Burslem G.M., Kyle H.F., Breeze A.L., Edwards T.A., Nelson A., Warriner S.L., Wilson A.J. Small-molecule proteomimetic inhibitors of the HIF-1alpha-p300 protein-protein interaction. ChemBioChem 2014, 15:1083-1087.
40. Lee T.K., Ahn J.M. Solid-phase synthesis of tris-benzamides as alpha-helix mimetics. ACS Comb Sci 2011, 13:107-111.
41. Barnard A., Long K., Yeo D.J., Miles J.A., Azzarito V., Burslem G.M., Prabhakaran P.T., Wilson A.E.A.J. Orthogonal functionalisation of alpha-helix mimetics. Org Biomol Chem 2014, 12:6794-6799.
42. Kushal S., Lao B.B., Henchey L.K., Dubey R., Mesallati H., Traaseth N.J., Olenyuk B.Z., Arora P.S. Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling. Proc Natl Acad Sci U S A 2013, 110:15602-15607.
43. Yap J.L., Cao X., Vanommeslaeghe K., Jung K.Y., Peddaboina C., Wilder P.T., Nan A., MacKerell A.D., Smythe W.R., Fletcher S. Relaxation of the rigid backbone of an oligoamide-foldamer-based alpha-helix mimetic: identification of potent bcl-xl inhibitors. Org Biomol Chem 2012, 10:2928-2933.
44. Shahian T., Lee G.M., Lazic A., Arnold L.A., Velusamy P., Roels C.M., Guy R.K., Craik C.S. Inhibition of a viral enzyme by a small-molecule dimer disruptor. Nat Chem Biol 2009, 5:640-646.
45. Lu F., Chi S.W., Kim D.H., Han K.H., Kuntz I.D., Guy R.K. Proteomimetic libraries: design, synthesis, and evaluation of p53-Mdm2 interaction inhibitors. J Comb Chem 2006, 8:315-325.
46. Saraogi I., Hebda J.A., Becerril J., Estroff L.A., Miranker A.D., Hamilton A.D. Synthetic alpha-helix mimetics as agonists and antagonists of islet amyloid polypeptide aggregation. Angew Chem Int Ed Engl 2010, 49:736-739.
47. Hassanpour A., De Carufel C.A., Bourgault S., Forgione P. Synthesis of 2,5-diaryl-substituted thiophenes as helical mimetics: towards the modulation of islet amyloid polypeptide (IAPP) amyloid fibril formation and cytotoxicity. Chemistry 2014, 20:2522-2528.
48. Boltjes A., Huang Y., van de Velde R., Rijkee L., Wolf S., Gaugler J., Lesniak K., Guzik K., Holak T.A., Domling A. Fragment-based library generation for the discovery of a peptidomimetic p53-Mdm4 inhibitor. ACS Comb Sci 2014, 16:393-396.
49. Cornette J.L., Cease K.B., Margalit H., Spouge J.L., Berzofsky J.A., DeLisi C. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J Mol Biol 1987, 195:659-685.
50. Marimganti S., Cheemala M.N., Ahn J.M. Novel amphiphilic alpha-helix mimetics based on a bis-benzamide scaffold. Org Lett 2009, 11:4418-4421.
51. Thompson S., Hamilton A.D. Amphiphilic alpha-helix mimetics based on a benzoylurea scaffold. Org Biomol Chem 2012, 10:5780-5782.
52. Jung K.Y., Vanommeslaeghe K., Lanning M.E., Yap J.L., Gordon C., Wilder P.T., Mackerell A.D., Fletcher S. Amphipathic alpha-helix mimetics based on a 1,2-diphenylacetylene scaffold. Org Lett 2013, 15:3234-3237.
53. Li X., Wang Z., Feng Y., Song T., Su P., Chen C., Chai G., Yang Y., Zhang Z. Two-face, two-turn alpha-helix mimetics based on a cross-acridine scaffold: analogues of the Bim BH3 domain. ChemBioChem 2014, 15:1280-1285.
54. Schafer G., Milic J., Eldahshan A., Gotz F., Zuhlke K., Schillinger C., Kreuchwig A., Elkins J.M., Abdul Azeez K.R., Oder A., Moutty M.C., et al. Highly functionalized terpyridines as competitive inhibitors of AKAP-PKA interactions. Angew Chem Int Ed Engl 2013, 52:12187-12191.
55. Campbell F., Plante J.P., Edwards T.A., Warriner S.L., Wilson A.J. N-alkylated oligoamide alpha-helical proteomimetics. Org Biomol Chem 2010, 8:2344-2351.
56. Lee J.H., Zhang Q., Jo S., Chai S.C., Oh M., Im W., Lu H., Lim H.S. Novel pyrrolopyrimidine-based alpha-helix mimetics: cell-permeable inhibitors of protein-protein interactions. J Am Chem Soc 2011, 133:676-679.
57. Oh M., Lee J.H., Wang W., Lee H.S., Lee W.S., Burlak C., Im W., Hoang Q.Q., Lim H.S. Potential pharmacological chaperones targeting cancer-associated mcl-1 and Parkinson disease-associated alpha-synuclein. Proc Natl Acad Sci U S A 2014, 111:11007-11012.
58. Rodriguez J.M., Hamilton A.D. Benzoylurea oligomers: synthetic foldamers that mimic extended alpha helices. Angew Chem Int Ed Engl 2007, 46:8614-8617.
59. Lee J.H., Lim H.S. Solid-phase synthesis of tetrasubstituted pyrrolo[2,3-d]pyrimidines. Org Biomol Chem 2012, 10:4229-4235.
60. Figliozzi G.M., Goldsmith R., Ng S.C., Banville S.C., Zuckermann R.N. Synthesis of n-substituted glycine peptoid libraries. Methods Enzymol 1996, 267:437-447.
61. Olivos H.J., Alluri P.G., Reddy M.M., Salony D., Kodadek T. Microwave-assisted solid-phase synthesis of peptoids. Org Lett 2002, 4:4057-4059.
62. Moon H., Lee W.S., Oh M., Lee H.S., Lee J.H., Im W., Lim H.S. Design, solid-phase synthesis, and evaluation of a phenyl-piperazine-triazine scaffold as alpha-helix mimetics. ACS Comb Sci 2014, 10.1021/co500114f.
63. Tosovska P., Arora P.S. Oligooxopiperazines as nonpeptidic alpha-helix mimetics. Org Lett 2010, 12:1588-1591.
64. Heeres J.T., Hergenrother P.J. High-throughput screening for modulators of protein-protein interactions: use of photonic crystal biosensors and complementary technologies. Chem Soc Rev 2011, 40:4398-4410.
65. Whitby L.R., Boyle K.E., Cai L., Yu X., Gochin M., Boger D.L. Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive alpha-helix mimetic library. Bioorg Med Chem Lett 2012, 22:2861-2865.
66. Lam K.S., Salmon S.E., Hersh E.M., Hruby V.J., Kazmierski W.M., Knapp R.J. A new type of synthetic peptide library for identifying ligand-binding activity. Nature 1991, 354:82-84.
67. Kodadek T. Rethinking screening. Nat Chem Biol 2010, 6:162-165.
68. Majmudar C.Y., Hojfeldt J.W., Arevang C.J., Pomerantz W.C., Gagnon J.K., Schultz P.J., Cesa L.C., Doss C.H., Rowe S.P., Vasquez V., Tamayo-Castillo G., et al. Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300. Angew Chem Int Ed Engl 2012, 51:11258-11262.
69. Lao B.B., Drew K., Guarracino D.A., Brewer T.F., Heindel D.W., Bonneau R., Arora P.S. Rational design of topographical helix mimics as potent inhibitors of protein-protein interactions. J Am Chem Soc 2014, 136:7877-7888.