Enhanced Permeability and Binding Activity of Isobutylene-Grafted Peptides
- Sun, S. 2
- Compañón, I. 1
- Martínez-Sáez, N. 2
- Seixas, J.D. 3
- Boutureira, O. 2
- Corzana, F. 1
- Bernardes, G.J.L. 23
-
1
Universidad de La Rioja
info
-
2
University of Cambridge
info
-
3
Universidade de Lisboa
info
ISSN: 1439-4227
Año de publicación: 2018
Volumen: 19
Número: 1
Páginas: 48-52
Tipo: Artículo
beta Ver similares en nube de resultadosOtras publicaciones en: Chembiochem : a European journal of chemical biology
Proyectos relacionados
Resumen
We present a new peptide-macrocyclization strategy with an isobutylene graft. The reaction is mild and proceeds rapidly and efficiently both for linear and cyclic peptides. The resulting isobutylene-grafted peptides possess improved passive membrane permeability due to the shielding of the polar backbone of the amides, as demonstrated by NMR spectroscopy and molecular dynamics simulations. The isobutylene-stapled structures are fully stable in human plasma and in the presence of glutathione. This strategy can be applied to bioactive cyclic peptides such as somatostatin. Importantly, we found that structural preorganization forced by the isobutylene graft leads to a significant improvement in binding. The combined advantages of directness, selectivity, and smallness could allow application to peptide macrocyclization based on this attachment of the isobutylene graft. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.