Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.
J Med Chem
; 40(21): 3408-22, 1997 Oct 10.
Article
en En
| MEDLINE
| ID: mdl-9341916
ABSTRACT
We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenoxiacetatos
/
Compuestos de Bencidrilo
/
Elastasa de Leucocito
/
Inhibidores Enzimáticos
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos