本研究旨在探討Naproxen酯類上醯基離去基對木瓜脂肪分解酵素水解動力分割影響。利用Naproxen甲酯、Naproxen乙酯、Naproxen三氟乙酯或Naproxen二甲基胺乙酯為反應基質，在不同溫度之極性含飽和水有機溶劑下反應，研究溶劑與溫度影響，並於45℃下含飽和水的異辛烷之較佳反應條件，進行酵素水解動力學探討。
本研究提出Michaelis-Menten之動力模式中，同時考慮產物醇所含胺、醇官能基，對酵素之活化與抑制作用，以解釋Naproxen酯類受酵素水解之行為。此外發現離去基誘導參數(inductive parameter)會影響酵素活性和選擇性。對有相同的誘導參數的Naproxen二甲基胺乙酯與Naproxen甲酯而言，兩者之酵素反應速率有四十倍的差距，推測可能原因為：二甲基胺乙基與酵素之過渡狀態具有額外氫鍵，造成四面中間分離形成醯化酵素中間體之反應速率變快。

The purpose of this research is aimed to investigate effects of the leaving group of (R,S)-naproxen ester on papaya lipase-catalyzed hydrolytic resolution. Hydrolytic resolution of (R,S)-naproxen esters (naproxen 2,2,2-trifluoroethly ester, naproxen ethyl ester, naproxen dimethylaminoethyl ester and naproxen methyl ester) in water-saturated organic solvents is employed as the model system for studying the effects of solvents and temperature on the lipase activity and enantioselectivity, where 45 ℃ and water-saturated isooctane are beneficial for giving better lipase activity and enantioselectivity. The kinetic analysis using a Michealis-Menten mechanism by coupled with product inhibition and activation was performed. The inductive parameter of leaving group has influence on the lipase activity and enantioselectivity. About 40-fold enhancement of the initial rate for (S)-esters was obtained between naproxen dimethylaminoethyl ester and naproxen methyl ester having the same inductive parameter of 0.01. The dimethylaminoethyl group may provide an additional hydrogen bond in the transition state of the acylation step, and then accelerate the bond-breaking of tetrahedral intermediate forming the acyl enzyme intermediate.

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