订书肽和小分子抑制癌蛋白-蛋白质相互作用的综述

Title:A Review of Stapled Peptides and Small Molecules to Inhibit Protein–Protein Interactions in Cancer

Volume: 23 Issue: 27

Author(s): Vidhya V. Iyer

Affiliation:

关键词: 小分子拮抗剂，癌症，蛋白质-蛋白质相互作用，订书肽，肽模拟物，α-螺旋

摘要: Disruption of binding of two or more molecules to a protein surface is a common basis of inhibition of many biological activities. Smallmolecule inhibitors, antibodies, proteins, and peptidomimetics have been examined as ways to antagonize receptor activity. The peptide α-helix plays a crucial role in the function of many proteins. Hence, much effort has been invested in mimicking α-helices at the binding interface of two proteins to competitively inhibit their interactions. Peptide stapling involves choosing two amino acids on the same face of a native peptide sequence for substitution with non-native amino acids whose side chains can be “stapled” together. The focus of this review is to survey the prevalence in literature of stapled peptides and small-molecule antagonists of interactions of selected mammalian cancer targets, such as β-catenin, BH3-only members of the Bcl-2 family of proteins, eIF4E/G, estrogen receptor complexes, EZH2, Mdm2, Notch, p110α, and survivin. The increasing interest in protein targets currently considered to be “undruggable” with greater selectivity for existing targets, with the goal of overcoming the omnipresent problem of resistance, could be served well by utilizing information about protein–protein interactions to develop both small-molecule and stapled peptide inhibitors.

Cite this article as:

Vidhya V. Iyer , A Review of Stapled Peptides and Small Molecules to Inhibit Protein–Protein Interactions in Cancer, Current Medicinal Chemistry 2016; 23 (27) . https://dx.doi.org/10.2174/0929867323666160627103134