Small and Simple, yet Sturdy: Conformationally Constrained Peptides with Remarkable Properties

The sheer size and vast chemical space (i.e., diverse repertoire and spatial distribution of functional groups) underlie peptides' ability to engage in specific interactions with targets of various structures. However, the inherent flexibility of the peptide chain negatively affects binding aff...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2021-02, Vol.22 (4), p.1611
Main Authors: Bozovičar, Krištof, Bratkovič, Tomaž
Format: Article
Language:English
Subjects:
Amino acids
Catalysts
Chains
Drug development
Flexibility
Functional groups
In vitro methods and tests
Libraries
Ligands
Molecular evolution
Peptides
Permeability
Polypeptides
Production methods
Proteins
Review
Spatial distribution
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The sheer size and vast chemical space (i.e., diverse repertoire and spatial distribution of functional groups) underlie peptides' ability to engage in specific interactions with targets of various structures. However, the inherent flexibility of the peptide chain negatively affects binding affinity and metabolic stability, thereby severely limiting the use of peptides as medicines. Imposing conformational constraints to the peptide chain offers to solve these problems but typically requires laborious structure optimization. Alternatively, libraries of constrained peptides with randomized modules can be screened for specific functions. Here, we present the properties of conformationally constrained peptides and review rigidification chemistries/strategies, as well as synthetic and enzymatic methods of producing macrocyclic peptides. Furthermore, we discuss the in vitro molecular evolution methods for the development of constrained peptides with pre-defined functions. Finally, we briefly present applications of selected constrained peptides to illustrate their exceptional properties as drug candidates, molecular recognition probes, and minimalist catalysts.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22041611