Depurination of synthetic poly(inosinic acid) analogues

A poly(inosinic acid) analogue, poly{[1'-(beta-hypoxanthine-9-yl)-5'-deoxy- D-erythro-pent-4'-enofuranose]-alt-[maleic acid]} (4), was synthesized by t he alternating copolymerization of nucleoside derivative 1 with maleic anhy dride and subsequent hydrolysis. N-Glycosidic bonds of the polymer were spo ntaneously hydrolyzed to liberate hypoxanthine from the polymer backbone in a buffer solution (pH 7.4) at room temperature. The depurination rate cons tant of the polymer at pH 7.4 and 37 degrees C was measured to be 1.9 x 10( -6) sec(-1), which was 10(5)-fold higher than that (3 x 10(-11) sec(-1)) of the depurination of DNA that occurred in the biological systems. The incre ase in the depurination rate was attributable to the high potential energy of the polymer caused by the crowded environment around the bases, so that the polymer was more susceptible to the hydrolysis. Since natural nucleic a cids often have compact structures with the crowded environment around the bases by the intricate chain folding, the depurination may also be accelera ted in a similar manner in the biological system. (C) 1999 John Wiley & Son s, Inc.