科学者ら、癌の75%を煽る混沌としたタンパク質を手なずける(Scientists tame chaotic protein fueling 75% of cancers)

2024-01-04 カリフォルニア大学リバーサイド校(UCR)

<関連情報>

• https://news.ucr.edu/articles/2024/01/04/scientists-tame-chaotic-protein-fueling-75-cancers
• https://pubs.acs.org/doi/10.1021/jacs.3c09615

立体多様化二環式ペプチドライブラリーから創製されたMYC標的阻害剤 MYC-Targeting Inhibitors Generated from a Stereodiversified Bicyclic Peptide Library

Zhonghan Li, Yi Huang, Ta I Hung, Jianan Sun, Desiree Aispuro, Boxi Chen, Nathan Guevara, Fei Ji, Xu Cong, Lingchao Zhu, Siwen Wang, Zhili Guo, Chia-en Chang, and Min Xue
Journal of the American Chemical Society  Published:January 3, 2024
DOI:https://doi.org/10.1021/jacs.3c09615

Abstract

Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E₃₆₃-R₃₇₈ epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.