摘要：

a hydrogen from the deoxyribose backbone of each op- posed strand to give carbon-centered radicals that, in turn, (4) scavenge dissolved oxygen to initiate a cascade of reactions leading ultimately to the observed cleavages. In this paper we present solution N M R studies that demonstrate for the first time the existence of intermediate 2 and provide an estimate of its lifetime at physiological temperature. These findings permit formulation of an overall kinetic scheme for the reaction of calicheamicin with DNA that frames specific questions about the relative importance of kinetic and thermodynamic factors in the sequence selectivity of its cleavages.Variable-temperature N M R experiments were undertaken to examine the behavior of the proposed intermediates between 1 and 4. Methyl thioglycolate (8 equiv, 14 mM) and triethylamine ( 5 equiv) were added to a methan01-d~s~olution of calicheamicin yI' (1.6 mM) at -72 OC. Despite the deceptively simple pseu- do-first-order disappearance of the methyl trisulfide resonance at 6 2.50 ( k = 2~ X IO4 s-I), the sulfur chemistry that occurred was obviously complex. The appearance of multiple signals for H-4, H-5, and H-8 indicated the presence of a variety of cali- cheamicin-derived species, while in the upfield region of the NMR spectrum, several methylthio-containing compounds were visible, which equilibrated to the methyl disulfide of methyl thioglycolate (RSSCH3,6 2.44)a This reaction manifold was monitored further

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