Depyrimidination of synthetic poly(uridylic acid) analogue

✍ Scribed by Man Jung Han; Tae Joon Cho; Ki Ho Kim; Kyung Soo Yoo; Young Dong Park; Ji Young Chang

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 186 KB
• Volume: 38
• Category: Article
• ISSN: 0887-624X
• DOI: 10.1002/(sici)1099-0518(20000201)38:3<423::aid-pola5>3.0.co;2-r

✦ Synopsis

A poly(uridylic acid) analogue, poly{[1Ј-(␤-uracil-1-yl)-5Ј-deoxy-D-erythropent-4Ј-enofuranose]-alt-[maleic acid]} (3), was synthesized by the alternating copolymerization of nucleoside derivative 1 and maleic anhydride and subsequent hydrolysis. N-glycosidic bonds of the polymer were hydrolyzed spontaneously to liberate uracil from the polymer backbone in a buffer solution (pH 7.4) at room temperature. The depyrimidination rate constant of the polymer at pH 7.4 at 80 °C was 8.2 ϫ 10 Ϫ5 s Ϫ1 , which was 10 4 times higher than that of the depyrimidination of DNA (1.2 ϫ 10 Ϫ9 s Ϫ1 ) under the same condition. The activation energy for the depyrimidination was 16 kcal/mol, which was about half of that for the relevant nucleoside reactions. The increase in the depyrimidination 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. Because natural nucleic acids often have compact structures with a crowded environment around the bases by an intricate chain folding, the pyrimidination also may have been accelerated in a similar manner in the biological system.