Small and simple, yet sturdy : conformationally constrained peptides with remarkable properties

Bozovičar, Krištof (author), Bratkovič, Tomaž (author)

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.

• Language: English
• Keywords: constrained peptides, macrocycles, crosslinking, enzymatic cyclization, stapling, hairpin loop
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 25 str.
• Numbering: Vol. 22, iss. 4, art. 1611
• PID: 20.500.12556/RUL-134890
• UDC: 543.645.6:615
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22041611
• COBISS.SI-ID: 50385155
• Publication date in RUL: 10.02.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 05.02.2021

Secondary language

• Language: Slovenian
• Keywords: peptidi

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P4-0127
• Name: Farmacevtska biotehnologija: znanost za zdravje