Hybridization-promoted and cytidine-selective activation for cross-linking with the use of 2-amino-6-vinylpurine derivatives.

Recently, we have proposed a new concept for cross-linking agents with inducible reactivity, in which the highly reactive cross-linking agent, the 2-amino-6-vinylpurine nucleoside analogue (1), can be regenerated in situ from its stable precursors, the phenylsulfide (4) and the phenylsulfoxide (3) derivatives, by a hybridization-promoted activation process with selectivity to cytidine. The phenylsulfide precursor (4) exhibited cross-linking ability despite its high stability toward strong nucleophiles such as amines and thiols. In this study, we investigated the substituent effects of the phenylsulfide group on the cross-linking reaction, and determined the 2-carboxy substituent of the phenylsulfide derivative (11k) as an efficient cross-linking agent with inducible reactivity. Detailed investigations have shown that the phenylsulfoxide (3) and phenylsulfide (4) precursors produce the 2-amino-6-vinylpurine nucleoside (1) as the common reactive species. It has been concluded that the nature of the inducibl...