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

Autor: Minglong Liu, Ryoji Yoshisada, Avand Amedi, Antonius J. P. Hopstaken, Mirte N. Pascha, Cornelis A. M. de Haan, Daan P. Geerke, David A. Poole, Seino A. K. Jongkees
Přispěvatelé: AIMMS, Chemistry and Pharmaceutical Sciences, Molecular and Computational Toxicology
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Liu, M, Yoshisada, R, Amedi, A, Hopstaken, A J P, Pascha, M N, de Haan, C A M, Geerke, D P, Poole, D A & Jongkees, S A K 2023, ' An Efficient, Site-Selective and Spontaneous Peptide Macrocyclisation During in vitro Translation ', Chemistry-A European Journal, vol. 29, no. 14, e202203923, pp. 1-9 . https://doi.org/10.1002/chem.202203923
Chemistry-A European Journal, 29(14):e202203923, 1-9. Wiley-VCH Verlag
ISSN: 1521-3765
0947-6539
DOI: 10.1002/chem.202203923
Popis: Macrocyclisation provides a means of stabilising the conformation of peptides, often resulting in improved stability, selectivity, affinity, and cell permeability. In this work we report a new approach to peptide macrocyclisation using a cyanobenzothiazole-containing amino acid that we show 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. Using molecular dynamics simulation we 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.
Databáze: OpenAIRE
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