Reactions of nucleic acid bases with alpha-acetylenic esters. Chemical modification of poly(A) and poly(C)

The reaction of chlorotetrolic (4-chloro-2-butynoic) esters with adenine and cytosine derivatives, in which a new heterocycle bearing an alkylating chloromethyl side chain is fused to the purine or pyrimidine ring, was extended to poly(A) and poly(C) used as models of nucleic acids. The derivatization proceeds under mild conditions and its extent can be controlled by the reaction time. The additional rings can exist in two isomeric forms and the nature of the isomer formed depends on steric factors in the vicinity of the reacting base. The reaction with chlorotetrolic esters discriminates between the single-stranded (reactive) and double-stranded (unreactive) forms, between the exposed an hidden adenine and cytosine bases and even between the exposed and sterically hindered fragments of the base moiety and thus allows structural investigations of these nucleic acids. The chloromethyl group of the derivatized nucleobases can be used to bind the modified polymers to other molecules.