Intermolecular and Intramolecular Catalysis in Deamination of Cytosine Nucleosides

Abstract

The rates of deamination of arabinosylcytosine (Ara-C), cytidine (Cyd) and cytosine (C) are compared in the presence and in the absence of catalytic buffers. Ratios of the rate constants in the absence of intermolecular catalysis by buffers indicate intramolecular catalysis by the 2′-hydroxyl in Ara-C. For example, the ratio of the deamination rate constants at pH 4.7, 70° is 53/1.4/1 for Ara-C/Cyd/C. In contrast to Cyd and C which show catalysis by both the acidic and basic components of the buffers, Ara-C exhibits only general-acid catalysis. These data suggest that intramolecular participation by the 2′-hydroxyl in Ara-C replaces the general-base catalytic role which the buffers perform in the deamination of C and Cyd. Mechanisms for inter- and intramolecular catalysis in the deamination of Ara-C, Cyd, and C are discussed.