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Approaches for peptide and protein cyclisation

Hayes, Heather C., Luk, Louis Y. P. ORCID: and Tsai, Yu-Hsuan ORCID: 2021. Approaches for peptide and protein cyclisation. Organic and Biomolecular Chemistry 19 (18) , pp. 3983-4001. 10.1039/D1OB00411E

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The cyclisation of polypeptides can play a crucial role in exerting biological functions, maintaining stability under harsh conditions and conferring proteolytic resistance, as demonstrated both in nature and in the laboratory. To date, various approaches have been reported for polypeptide cyclisation. These approaches range from the direct linkage of N- and C- termini to the connection of amino acid side chains, which can be applied both in reaction vessels and in living systems. In this review, we categorise the cyclisation approaches into chemical methods (e.g. direct backbone cyclisation, native chemical ligation, aldehyde-based ligations, bioorthogonal reactions, disulphide formation), enzymatic methods (e.g. subtiligase variants, sortases, asparaginyl endopeptidases, transglutaminases, non-ribosomal peptide synthetases) and protein tags (e.g. inteins, engineered protein domains for isopeptide bond formation). The features of each approach and the considerations for selecting an appropriate method of cyclisation are discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Cardiff Catalysis Institute (CCI)
Publisher: Royal Society of Chemistry
ISSN: 1477-0520
Funders: EPSRC, BBSRC and Royal Society
Date of First Compliant Deposit: 6 May 2021
Date of Acceptance: 1 April 2021
Last Modified: 07 Jul 2023 19:06

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