Total synthesis of [Ψ[C(âNH)NH]Tpg(4)]vancomycin and its (4-chlorobiphenyl)methyl derivative: impact of peripheral modifications on vancomycin analogues redesigned for dual D-Ala-D-Ala and D-Ala-D-Lac binding.
J Am Chem Soc
; 136(39): 13522-5, 2014 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-25211770
ABSTRACT
The total synthesis of two key analogues of vancomycin containing single-atom exchanges in the binding pocket (residue 4 amidine and thioamide) are disclosed as well as their peripherally modified (4-chlorobiphenyl)methyl (CBP) derivatives. Their assessment indicates that combined pocket amidine and CBP peripherally modified analogues exhibit a remarkable spectrum of antimicrobial activity (VSSA, MRSA, VanA and VanB VRE) and impressive potencies (MIC = 0.06-0.005 µg/mL) against both vancomycin-sensitive and -resistant bacteria and likely benefit from two independent and synergistic mechanisms of action. Like vancomycin, such analogues are likely to display especially durable antibiotic activity not prone to rapidly acquired clinical resistance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vancomicina
/
Alanina
/
Dipeptídeos
/
Lactatos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article