Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analogue N-oxaloglycine and its derivatives.
J Med Chem
; 35(14): 2652-8, 1992 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-1321909
N-Oxaloglycine (3) is an alpha-ketoglutarate (1) analogue that is a competitive inhibitor of prolyl 4-hydroxylase (EC 1.14.11.2). A study of the structure-activity relationships of some other oxalo derivatives shows that substitution on the glycine moiety modulates activity stereoselectively and that if the omega-carboxylate is homologated or replaced by either acylsulfonamides or anilide, then activity is sharply reduced. This sensitivity to these changes is contrasted with the relative insensitivity of another putative alpha-ketoglutarate analogue, pyridine-2,5-dicarboxylic acid (2), and the implication is discussed that compounds of both series are unlikely to bind to prolyl hydroxylase in the same way even though both inhibit the enzyme competitively.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Procolágeno-Prolina Dioxigenasa
/
Aminoácidos Dicarboxílicos
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1992
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Estados Unidos