Molecular mechanism of thymidylate synthase-catalysed reaction and interaction of the enzyme with 2- and-or 4-substituted analogues of dUMP and 5-fluoro-dUMP

• Autorzy: Rode W. , Les A.
• Języki publikacji: EN

Abstrakty

EN

Thymidylate synthase is a target enzyme in anticancer, antiviral, antifungal and antiprotozoan chemotherapy. With two dUMP analogues, 5-fluoro-dUMP (FdUMP) and 5-(trifluoromethyl)-dUMP (CF3dUMP), strong thymidylate synthase inhibitors and active forms of drugs, the inhibition mechanism is based on the reaction mechanism. Recent comparative studies of new dUMP analogues, containing more than one substituent in the pyrimidine ring, showed that substitution of the pyrimidine ring Qd=0 group in FdUMP by either C(4)=N-OH group (in N4-hydroxy-FdCMP) or C(4)=S group (in 4-thio-FdUMP) preserves high inhibitory potency of the drug but may alter its specificity for thymidylate synthases from various sources, which differ in sensitivity to slow-binding inhibition by FdUMP. Informations suggesting mechanisms responsible for the foregoing have been reviewed, including results of molecular modeling studies suggesting interaction of the pyrimidine C(4)=0 group, or its modification, with the N4-methylene-

Słowa kluczowe

EN

chemotherapy; enzyme; thymidylate synthase; anticancer chemotherapy; drug active form; antiviral chemotherapy; antifungal chemotherapy; inhibition specificity

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1996
• Tom: 43
• Numer: 1
• Opis fizyczny: p.133-142

Twórcy

autor

Rode W.

• Polish Academy of Sciences, L.Pasteur 3, 02-093 Warsaw, Poland

autor

Les A.

Bibliografia

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