Pharmacophore-guided lead optimization: the rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease.
Bioorg Med Chem Lett
; 19(19): 5811-3, 2009 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-19703771
ABSTRACT
Botulinum neurotoxins, responsible for the neuroparalytic syndrome botulism, are the deadliest of known biological toxins. The work described in this study was based on a three-zone pharmacophore model for botulinum neurotoxin serotype A light chain inhibition. Specifically, the pharmacophore defined a separation between the overlaps of several different, non-zinc(II)-coordinating small molecule chemotypes, enabling the design and synthesis of a new structural hybrid possessing a Ki=600 nM (+/-100 nM).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Toxinas Botulínicas Tipo A
/
Neurotoxinas
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article