Small and simple, yet sturdy

conformationally constrained peptides with remarkable properties

Krištof Bozovičar (Author), Tomaž Bratkovič (Author)

Abstract

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.

Keywords

constrained peptides;macrocycles;crosslinking;enzymatic cyclization;stapling;hairpin loop;

Data

Language:	English
Year of publishing:	2021
Typology:	1.02 - Review Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	543.645.6:615
COBISS:	50385155
ISSN:	1422-0067
Views:	167
Downloads:	60
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	Peptidi;
Type (COBISS):	Article
Pages:	str. 1-25
Volume:	ǂVol. ǂ22
Issue:	ǂiss. ǂ4
Chronology:	2021
DOI:	10.3390/ijms22041611
ID:	14495768