Synthesis and evaluation of chlorinated substrate analogues for farnesyl diphosphate synthase.
Synthesis and evaluation of chlorinated substrate analogues for farnesyl diphosphate synthase.
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法尼基二磷酸合酶氯化底物类似物的合成和评价。
DOI：
10.1021/jo1024305
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Poulter,CDale
中科院分区：
文献类型：
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作者：
Heaps,NicoleA;Poulter,CDale
合成了异戊烯基二磷酸(IPP)和二甲基烯丙基二磷酸(DMAPP)的底物类似物，其中C3甲基被氯取代，并作为禽法呢基二磷酸合成酶(FPPase)的底物进行了评价。IPP类似物(3-Clipp)与二甲基烯丙基二磷酸(DMAPP)或香叶基二磷酸(GPP)温育后，分别得到相应的香叶基二磷酸(3-ClGPP)和法尼基二磷酸(3-ClFPP)的氯化类似物。在3-ClIPP和3-ClDMAPP的孵育中未检测到产物。以3-ClDMAPPgave11-ClFP为唯一产物孵育IPP。KM3-ClipP(带有DMAPP)和KM3-ClDMAPP(带有IPP)的值与IPP和DMAPP的值相似；但两个类似物的Kcat值都大大降低。这些结果与解离亲电烷基化机理一致，其中限速步骤从烯丙基底物中碳−氧键的异解断裂转变为高烯丙基底物双键的烷基化。
Substrate analogues for isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where the C3 methyl groups were replaced by chlorine, were synthesized and evaluated as substrates for avian farnesyl diphosphate synthase (FPPase). The IPP analogue (3-ClIPP)was a cosubstrate when incubated with dimethylallyl diphosphate (DMAPP) or geranyl diphosphate (GPP) to give the corresponding chlorinated analogues of geranyl diphosphate (3-ClGPP) and farnesyl diphosphate (3-ClFPP), respectively. No products were detected in incubations of3-ClIPPwith3-ClDMAPP. Incubation of IPP with3-ClDMAPPgave11-ClFPPas the sole product. Values of KM3-ClIPP(with DMAPP) and KM3-ClDMAPP(with IPP) were similar to those for IPP and DMAPP; however, values ofkcatfor both analogues were substantially lower. These results are consistent with a dissociative electrophilic alkylation mechanism where the rate-limiting step changes from heterolytic cleavage of the carbon−oxygen bond in the allylic substrate to alkylation of the double bond of the homoallylic substrate.