Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

Angelastro, Antonio ORCID: https://orcid.org/0000-0002-4023-7411, Bargh, Jonathan, Guria, Subhajit, Laserna, Victor and Luk, Louis ORCID: https://orcid.org/0000-0002-7864-6261 2026. Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies. Beilstein Journal of Organic Chemistry 22 , pp. 857-881. 10.3762/bjoc.22.67

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Abstract

Site-specific modifications of native-sequence proteins are technologies that underpin progresses in chemical biology, diagnostics and next-generation biotherapeutics. However, the pursuit of site-specificity has often come at the expense of scalability and usability, ultimately limiting translational potential of a modification tool. This review critically compares current key strategies, including terminal, disulfide-rebridging, small-molecule, glycan and enzyme-based modifications. Finally, we present a decision tree for method selection and highlight opportunities for innovation in next-generation native-sequence protein modification technologies. [Abstract copyright: Copyright © 2026, Angelastro et al.]

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Chemistry
Publisher:	Beilstein-Institut
ISSN:	1860-5397
Date of First Compliant Deposit:	2 July 2026
Date of Acceptance:	22 April 2026
Last Modified:	02 Jul 2026 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/187876

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