MYC-Targeting Inhibitors Generated from a Stereodiversified Bicyclic Peptide Library.

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 tr

SUBMITTER: Li Z 

PROVIDER: S-EPMC10797614 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature