ORCID ID

https://orcid.org/0000-0003-4188-0633

Document Type

Article

Publication Date

3-2023

Publication Title

Molecules

Disciplines

Biology

Abstract

The study of peptides (synthetic or corresponding to discrete regions of proteins) has facilitated the understanding of protein structure-activity relationships. Short peptides can also be used as powerful therapeutic agents. However, the functional activity of many short peptides is usually substantially lower than that of their parental proteins. This is (as a rule) due to their diminished structural organization, stability, and solubility often leading to an enhanced propensity for aggregation. Several approaches have emerged to overcome these limitations, which are aimed at imposing structural constraints into the backbone and/or sidechains of the therapeutic peptides (such as molecular stapling, peptide backbone circularization and molecular grafting), therefore enforcing their biologically active conformation and thus improving their solubility, stability, and functional activity. This review provides a short summary of approaches aimed at enhancing the biological activity of short functional peptides with a particular focus on the peptide grafting approach, whereby a functional peptide is inserted into a scaffold molecule. Intra-backbone insertions of short therapeutic peptides into scaffold proteins have been shown to enhance their activity and render them a more stable and biologically active conformation.

DOI

10.3390/molecules28052383

Version

Publisher's PDF

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Volume

28

Issue

5

Included in

Biology Commons

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