PubReading [149] - Therapeutic design of peptide modulators of protein-protein interactions in membranes - T. Stone and C. Deber

Membrane proteins play the central roles in a variety of cellular processes, ranging from nutrient uptake and signalling, to cell-cell communication. Their biological functions are directly related to how they fold and assemble; defects often lead to disease. Protein–protein interactions (PPIs) within the membrane are therefore of great interest as therapeutic targets. Here we review the progress in the application of membrane–insertable peptides for the disruption or stabilization of membrane–based PPIs. We describe the design and preparation of transmembrane peptide mimics; and of several categories of peptidomimetics used for study, including D-enantiomers, non–natural amino acids, peptoids, and β-peptides. Further aspects of the review describe modifications to membrane–insertable peptides, including lipidation and cyclization via hydrocarbon stapling. These approaches provide a pathway toward the development of metabolically stable, non-toxic, and efficacious peptide modulators of membrane–based PPIs. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid- control of protein activity edited by Dirk Schneider.doi.org/10.1016/j.bbamem.2016.08.013 - 2017