Issue 7, 2024

Biocompatible strategies for peptide macrocyclisation

Abstract

Peptides are increasingly important drug candidates, offering numerous advantages over conventional small molecules. However, they face significant challenges related to stability, cellular uptake and overall bioavailability. While individual modifications may not address all these challenges, macrocyclisation stands out as a single modification capable of enhancing affinity, selectivity, proteolytic stability and membrane permeability. The recent successes of in situ peptide modifications during screening in combination with genetically encoded peptide libraries have increased the demand for peptide macrocyclisation reactions that can occur under biocompatible conditions. In this perspective, we aim to distinguish biocompatible conditions from those well-known examples that are fully bioorthogonal. We introduce key strategies for biocompatible peptide macrocyclisation and contextualise them within contemporary screening methods, providing an overview of available transformations.

Graphical abstract: Biocompatible strategies for peptide macrocyclisation

Supplementary files

Article information

Article type
Perspective
Submitted
27 Oct 2023
Accepted
04 Jan 2024
First published
05 Jan 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 2300-2322

Biocompatible strategies for peptide macrocyclisation

J. He, P. Ghosh and C. Nitsche, Chem. Sci., 2024, 15, 2300 DOI: 10.1039/D3SC05738K

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