Synthetic inhibitors of Escherichia coli, calf thymus, and Ehrlich ascites tumor thymidylate synthetase.
J Med Chem
; 19(7): 903-8, 1976 Jul.
Article
in En
| MEDLINE
| ID: mdl-781246
ABSTRACT
In a study of active site binding the inhibition of thymidylate synthetase derived from Escherichia coli, calf thymus, and Ehrlich ascites tumor was examined using eight inhibitors. 5-Substituted 2'-deoxyuridine 5'-phosphate analogues used in this study are the hydroxymethyl, methoxymethyl, benzyloxymethyl, formyl, acetyl, allyl, and two potential active site alkylating substituents 2,3-oxypropyl and the azidomethyl analogues. All compounds were competitive with the substrate, 2'-deoxyuridine 5'-phosphate; the most potent inhibitor was 5-formyl-dUMP (Ki = 0.1, 0.09, and 0.08 muM for the respective enzyme). The 5-hydroxymethyl, 5-benzyloxymethyl, and 5-azidomethyl derivatives of dUMP showed some differential inhibition; these compounds were two to three times more active against the ascites tumor enzyme than against the thymus enzyme.
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Database:
MEDLINE
Main subject:
Thymidylate Synthase
/
Thymus Gland
/
Uracil Nucleotides
/
Carcinoma, Ehrlich Tumor
/
Escherichia coli
/
Methyltransferases
Limits:
Animals
Language:
En
Year:
1976
Type:
Article