The Influence of Disulfide, Thioacetal and Lanthionine-Bridges on the Conformation of a Macrocyclic Peptide.

Autor: Darling WTP; Department of Chemistry, University College London, 20, Gordon Street, London, WC1H 0AJ, UK., Wieske LHE; Department of Chemistry-BMC, Uppsala University, SE-751 23, Uppsala, Sweden., Cook DT; Department of Chemistry, University College London, 20, Gordon Street, London, WC1H 0AJ, UK., Aliev AE; Department of Chemistry, University College London, 20, Gordon Street, London, WC1H 0AJ, UK., Caron L; Biosynth Laboratories Ltd (formerly Cambridge Research Biochemicals Ltd), 17-18 Belasis Court, Belasis Hall Technology Park, Billingham, TS23 4AZ, UK., Humphrys EJ; Biosynth Laboratories Ltd (formerly Cambridge Research Biochemicals Ltd), 17-18 Belasis Court, Belasis Hall Technology Park, Billingham, TS23 4AZ, UK., Figueiredo AM; Department of Structural and Molecular Biology, Division of Biosciences, University College London, UCL Darwin Building, Gower Street, London, WC1E 6BT, UK., Hansen DF; Department of Structural and Molecular Biology, Division of Biosciences, University College London, UCL Darwin Building, Gower Street, London, WC1E 6BT, UK., Erdélyi M; Department of Chemistry-BMC, Uppsala University, SE-751 23, Uppsala, Sweden., Tabor AB; Department of Chemistry, University College London, 20, Gordon Street, London, WC1H 0AJ, UK.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Sep 05; Vol. 30 (50), pp. e202401654. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1002/chem.202401654
Abstrakt: Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1-7), incorporating either disulfide, or non-reducible thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine-tune the conformational properties of cyclic peptides, which may modulate their bioactivities.
(© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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