Rational Design and Synthesis of Right-Handed D-Sulfono-γ-AApeptide Helical Foldamers As Potent Inhibitors of Protein-Protein Interactions

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Jul 24

PMID 32700908

Citations 14

Authors

Peng Sang

Yan Shi

Pirada Higbee

Minghui Wang

Sami Abdulkadir

Junhao Lu

Gary Daughdrill

Jiandong Chen

Jianfeng Cai

Affiliations

Soon will be listed here.

Abstract

Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed d-sulfono-γ-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformation to α-peptides, making them an ideal molecular scaffold to design α-helical mimetics. As demonstrated with p53-MDM2 PPI as a model application, the right-handed d-sulfono-γ-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The design of d-sulfono-γ-AApeptides may provide a new and alternative strategy to modulate protein-protein interactions.

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