Poly(2-amino-8-methyldeoxyadenylic acid): contrasting effects in deoxy- and ribopolynucleotides of 2-amino and 8-methyl substituents.

Poly(2-amino-8-methyldeoxyadenylic acid) interacts readily with pyrimidine polynucleotides to form double helices only slightly less stable than those in which the purine polymer lacks the 8-Me group. In the ribo series, by contrast, complexes formed with poly(2-amino-8-methyladenylic acid) are very strongly destabilized by the 8-Me group, despite a larger stabilizing effect of the 2-NH2 group in the ribo series. These results are interpreted in terms of a smaller steric interference of the 8-Me group with 2'-CH2 than with 2'-CHOH, leading to a smaller population of syn structures in the deoxy chain and a consequent lower interference with homopolymer duplex formation. UV, circular dichroism (CD), and IR spectra of the new polymer and its complexes are reported and related to structural and energetic characteristics of the molecules. Since direct synthesis of 2-amino-8-methyldeoxyadenosine was not feasible, the corresponding riboside was prepared, the 3'- and 5'-positions were protected with a disilyloxy group, and a 2'-[(imidazol-1-yl)thiocarbonyl] group was introduced. Reduction with tributyltin hydride followed by deprotection gave the nucleoside, which was then converted to the triphosphate by standard methods. The homopolymer was prepared with terminal deoxynucleotidyl transferase.