Novel all-hydrocarbon stapled p110α[E545K] peptides as blockers of the oncogenic p110α[E545K]-IRS1 interaction.
作者： Xiao Hu , Yanhua He , Liping Wu , Yujun Hao , Zhenghe Wang
DOI: 10.1016/J.BMCL.2017.10.076
关键词:
摘要: Abstract To follow up on our recent discovery of the 18-amino acid all-hydrocarbon [i, i + 4]-stapled p110α[E545K] peptide 1 that was shown to potently block intracellular p110α[E545K]-IRS1 interaction (a protein-protein uniquely present in cancer cells expressing p110α[E545K]) and growth xenograft tumors formed by cancers harboring this mutation, current study we prepared examined six derivatives 1, i.e. stapled peptides 2-A, 2-B, 3-A, 3-B, 4-A, 4-B. We found that 4-B had higher % α-helicity than 1; moreover, enhanced also led an proteolytic stability. When compared with structurally simplified 14-amino 4-A were more deactivate AKT phosphorylation at Ser473 p110α[E545K]-expressing colon cells, whose activation previously demonstrated us be specifically derived from interaction. The preliminary findings have laid a foundation for future extensive studies newly identified study.
sci-hub.se 参考文章(10)
Gregory H. Bird, Federico Bernal, Kenneth Pitter, Loren D. Walensky, Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains. Methods in Enzymology. ,vol. 446, pp. 369- 386 ,(2008) , 10.1016/S0076-6879(08)01622-4
Y He, D Chen, W Zheng, An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide 'stapling' technology. Oncogene. ,vol. 34, pp. 5685- 5698 ,(2015) , 10.1038/ONC.2015.37
C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, L. M. Amzel, The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations Science. ,vol. 318, pp. 1744- 1748 ,(2007) , 10.1126/SCIENCE.1150799
Yujun Hao, Chao Wang, Bo Cao, Brett M. Hirsch, Jing Song, Sanford D. Markowitz, Rob M. Ewing, David Sedwick, Lili Liu, Weiping Zheng, Zhenghe Wang, Gain of Interaction with IRS1 by p110α-Helical Domain Mutants Is Crucial for Their Oncogenic Functions Cancer Cell. ,vol. 23, pp. 583- 593 ,(2013) , 10.1016/J.CCR.2013.03.021
Jack C. Slootweg, Johan Kemmink, Rob M. J. Liskamp, Dirk T. S. Rijkers, Synthesis and structural characterization of the individual diastereoisomers of a cross-stapled alkene-bridged nisin DE-ring mimic. Organic and Biomolecular Chemistry. ,vol. 11, pp. 7486- 7496 ,(2013) , 10.1039/C3OB41359D
Young-Woo Kim, Tom N Grossmann, Gregory L Verdine, Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis Nature Protocols. ,vol. 6, pp. 761- 771 ,(2011) , 10.1038/NPROT.2011.324
Elizaveta S. Leshchiner, Andrey Parkhitko, Gregory H. Bird, James Luccarelli, Joseph A. Bellairs, Silvia Escudero, Kwadwo Opoku-Nsiah, Marina Godes, Norbert Perrimon, Loren D. Walensky, Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 1761- 1766 ,(2015) , 10.1073/PNAS.1413185112
Gerard J. Hilinski, Young-Woo Kim, Jooyeon Hong, Peter S. Kutchukian, Charisse M. Crenshaw, Shaunna S. Berkovitch, Andrew Chang, Sihyun Ham, Gregory L. Verdine, Stitched α-helical peptides via bis ring-closing metathesis. Journal of the American Chemical Society. ,vol. 136, pp. 12314- 12322 ,(2014) , 10.1021/JA505141J
Yana K. Rennie, Patrick J. McIntyre, Tito Akindele, Richard Bayliss, Andrew G. Jamieson, A TPX2 Proteomimetic Has Enhanced Affinity for Aurora-A Due to Hydrocarbon Stapling of a Helix. ACS Chemical Biology. ,vol. 11, pp. 3383- 3390 ,(2016) , 10.1021/ACSCHEMBIO.6B00727
Shreya Mitra, Jeffrey E. Montgomery, Matthew J. Kolar, Gang Li, Kang J. Jeong, Bo Peng, Gregory L. Verdine, Gordon B. Mills, Raymond E. Moellering, Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer Nature Communications. ,vol. 8, pp. 660- ,(2017) , 10.1038/S41467-017-00888-8