A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide.
Bioorg Med Chem Lett
; 42: 128027, 2021 06 15.
Article
en En
| MEDLINE
| ID: mdl-33839255
ABSTRACT
Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains. Here, we reported a facile strategy, inspired by native chemical ligation, for vancomycin C-terminus functionalization and derivatization. The introduction of C-terminal hydrazide on vancomycin not only provided us an accessible method for C-terminus functionalization through carbonyl azide and thioester, also acted as an efficient site for vancomycin structure modifications. Based on hydrazide-vancomycin, we effectively conjugated cysteine and cysteine containing peptides onto vancomycin C-terminus, and two fluorescent FITC-vancomycin were prepared through Cys-Maleimide conjugation. Meanwhile, we introduced lipophilic structures onto vancomycin C-terminus via the hydrazide moiety. The obtained vancomycin derivatives were evaluated against both Gram-positive and negative bacteria strains.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vancomicina
/
Staphylococcus aureus Resistente a Vancomicina
/
Hidrazinas
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article