Stabilized helical peptides: overview of the technologies and therapeutic promises

Abstract

Introduction: Helical structures in proteins and naturally occurring peptides play a major role in a variety of biological processes by mediating interactions with proteins and other macromolecules such as nucleic acids and lipid membranes. The use of short synthetic peptides encompassing helical segments to modulate or disrupt such interactions, when associated with human diseases, represents great pharmacological interest.

Areas covered: Multiple chemical approaches have been developed to increase the conformational and metabolic stabilities of helical peptides and to improve their biomedical potential. After a brief overview of these technologies and the most recent developments, this review will focus on the main therapeutic areas and targets and will discuss their promise.

Expert opinion: Potential benefits associated with increased helix stability extend beyond simple affinity enhancement. Some peptidomimetic helices are being endowed with features desirable for cellular activity such as increased resistance to proteolysis and/or cell permeability. Recent advances in the field of peptide and related peptidomimetic helices are not just conceptual, but are likely to be of practical utility in the process of optimizing peptides as clinical candidates, and developing medium-size therapeutics.

Keywords:

• antimicrobials
• apoptosis
• cell permeability
• foldamers
• helices
• peptide hormones
• peptidomimetics
• protein–protein interactions
• stapled peptides
• viral entry

Notes

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