An Efficient, Site-Selective and Spontaneous Peptide Macrocyclisation During in vitro Translation.

Autor: Liu M; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands., Yoshisada R; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands., Amedi A; Department Chemical Biology and Drug Discovery and Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, 3584 CG, the Netherlands., Hopstaken AJP; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands., Pascha MN; Section Virology Division of Infectious Diseases and Immunology Department of Biomolecular Health Sciences Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the Netherlands., de Haan CAM; Section Virology Division of Infectious Diseases and Immunology Department of Biomolecular Health Sciences Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the Netherlands., Geerke DP; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands., Poole DA 3rd; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands., Jongkees SAK; Chemistry and Pharmaceutical Sciences and Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, the Netherlands.; Department Chemical Biology and Drug Discovery and Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, 3584 CG, the Netherlands.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Mar 07; Vol. 29 (14), pp. e202203923. Date of Electronic Publication: 2023 Feb 06.
DOI: 10.1002/chem.202203923
Abstrakt: Macrocyclisation provides a means of stabilising the conformation of peptides, often resulting in improved stability, selectivity, affinity, and cell permeability. In this work, a new approach to peptide macrocyclisation is reported, using a cyanobenzothiazole-containing amino acid that can be incorporated into peptides by both in vitro translation and solid phase peptide synthesis, meaning it should be applicable to peptide discovery by mRNA display. This cyclisation proceeds rapidly, with minimal by-products, is selective over other amino acids including non N-terminal cysteines, and is compatible with further peptide elaboration exploiting such an additional cysteine in bicyclisation and derivatisation reactions. Molecular dynamics simulations show that the new cyclisation group is likely to influence the peptide conformation as compared to previous thioether-based approaches, through rigidity and intramolecular aromatic interactions, illustrating their complementarity.
(© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje