Deoxythymine monophosphate

Fig. 24.4 Thymidylate synthase (TS) biochemical pathway. dUMP-deoxyuridine monophosphate, dTMP-deoxythymine monophosphate, dTTP-deoxythymine triphosphate.

Of the two objectives (Section I) of investigations on the models of this cofactor, the one translating its functional capability of carbon transfers in the evolution of chemical synthesis has been amply illustrated. With respect to the second objective of providing support to the molecular mechanism of the enzymatic process in which this cofactor plays an essential role, Pandit chose to mimic in totality the thymidylate synthase (TS) catalyzed conversion of deoxyuridine monophosphate (dUMP, 129) to deoxythymine monophosphate (dTMP, 131) that is reported to proceed by transfer of a methylene group of an imidazolidine component of 1 to C-5 of dUMP 129, the nucleophilicity of which is enhanced by the addition of a thiol of apoenzyme at C-6, generating the methylene intermediate 130. The subsequent delivery of the C-6H of 1 as an hydride equivalent to the methylene carbon is followed by elimination of a thiol and formation of dTMP 131 along with 7,8-dihydrofolate 132. 

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