Constraining an Irregular Peptide Secondary Structure through Ring-Closing Alkyne Metathesis.

ABSTRACT: Macrocyclization can be used to constrain peptides in their bioactive conformations, thereby supporting target affinity and bioactivity. In particular, for the targeting of challenging protein-protein interactions, macrocyclic peptides have proven to be very useful. Available approaches focus on the stabilization of α-helices, which limits their general applicability. Here we report for the first time on the use of ring-closing alkyne metathesis for the stabilization of an irregular peptide secondary structure. A small library of alkyne-crosslinked peptides provided a number of derivatives with improved target affinity relative to the linear parent peptide. In addition, we report the crystal structure of the highest-affinity derivative in a complex with its protein target 14-3-3ζ. It can b

SUBMITTER: Cromm PM 

PROVIDER: S-EPMC5096054 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature