Azaphilones as Activation-Free Primary-Amine-Specific Bioconjugation Reagents for Peptides, Proteins and Lipids.
Angew Chem Int Ed Engl
; 61(6): e202111783, 2022 02 01.
Article
em En
| MEDLINE
| ID: mdl-34825445
ABSTRACT
Residue-selective bioconjugation methods for biomolecules are highly sought to expand the scope of their biological and medical applications. Inspired by the mechanism of the generation of natural vinylogous γ-pyridones (vPDNs), we have developed a novel unique azaphilone-based, activation-free primary-amine-selective bioconjugation method for biomolecules. Our strategy allows facile functionalization of primary amine groups in peptides and proteins, including the clinically used therapeutic antibody trastuzumab, by generating a highly stable vPDN linkage. Excellent chemoselectivity toward primary amines also enables the azaphilone derivatives to specifically modify the lipid components of Gram-positive bacteria while bypassing Gram-negative bacteria and mammalian cells. The new method shows significant advantages including chemoselectivity, efficiency, flexibility and biocompatibility, and therefore provides a valuable addition to the current toolbox for biomolecule conjugation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Pigmentos Biológicos
/
Piridonas
/
Benzopiranos
/
Proteínas
/
Aminas
/
Lipídeos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article