핵산 모델로서 Phosphate Diester들의 가수분해 반응

Hydrolysis of Phosphate Diesters as Nucleic Acid Model

RNA의 가수분해시에 생성되는 cyclic phosphate 중간체의 모델 화합물인 ethylene phosphate의 P-O결합 분해속도 상수는 $100^{\circ}C$ 에서 $k=3{\times}10^{-7}s^{-1}({\Delta}H{\neq}=24\;kcal,\;{\Delta}S{\neq}=25.5\;eu)$이었으며 DNA모델 화합물인 dimethylphosphate는 $150^{\circ}C$에서 $1{\times}10^{-11}s^{-1}({\Delta}H{\neq}=36\;kcal,\;{\Delta}S{\neq}=25.5\;eu)$이었다. RNA모델 화합물인 hydroxyethylmethylphosphate의 가수분해는 dimethylphosphate의 C-O결합이 가수분해되는 반응속도와 비교될 만한 정도의 반응속도가 관측되었다.

Rate of hydrolysis ethylene phosphate, dimethylphosphate and hydroxyethylmethylphosphate in neutral water have been measured. Hydrolysis of ethylene phosphate proceeds with P-0 bond cleavage $(k_{obs}=3{\times}10^{-7}s^{-1}\;at\;100^{\circ}C,\;{\Delta}H{\neq}=24\;kcal,\;{\Delta}S{\neq}=25.5\;eu)$. In constrast, hydrolysis of dimethylphosphate proceeds with C-O bond cleavage $(k_{obs}=3{\times}10^{-7}s^{-1}\;at\;150^{\circ}C)$. The rate constant for P-O bond cleavage of dimethylphosphate is estimated at $1{\times}10^{-11}s^{-1}\;at\;150^{\circ}C,\;({\Delta}H{\neq}=36\;kcal,\;{\Delta}S{\neq}=25.5\;eu)$. A phosphodiesterase catalyzed hydrolysis of dimethylphosphate is $10^{17}$ times faster than the simple water rate. The observed rate of hydrolysis of hydroxyethylmethylphosphate is comparable to that of dimethylphosphate indicating C-O bond cleavage $(k_{obs}=6{\times}10^{-7}s^{-1}\;at\;150^{\circ}C)$.