合成和评价法尼基二磷酸合酶的氯化底物类似物。
Synthesis and evaluation of chlorinated substrate analogues for farnesyl diphosphate synthase.
机构信息
Department of Chemistry, University of Utah, 315 South 1400 East RM 2020, Salt Lake City, Utah 84112, USA.
出版信息
J Org Chem. 2011 Mar 18;76(6):1838-43. doi: 10.1021/jo1024305. Epub 2011 Feb 24.
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 of 3-ClIPP with 3-ClDMAPP. Incubation of IPP with 3-ClDMAPP gave 11-ClFPP as the sole product. Values of K(M)(3-ClIPP) (with DMAPP) and K(M)(3-ClDMAPP) (with IPP) were similar to those for IPP and DMAPP; however, values of k(cat) for 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.
异戊烯二磷酸（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，被合成并评估为禽法尼基二磷酸合酶（FPPase）的底物。当与二甲基烯丙基二磷酸（DMAPP）或香叶基二磷酸（GPP）一起孵育时，IPP 类似物（3-ClIPP）是一种共底物，分别得到相应的氯代香叶基二磷酸（3-ClGPP）和法尼基二磷酸（3-ClFPP）。在 3-ClIPP 与 3-ClDMAPP 的孵育中未检测到产物。IPP 与 3-ClDMAPP 的孵育仅产生 11-ClFPP 作为唯一产物。K（M）（3-ClIPP）（与 DMAPP）和 K（M）（3-ClDMAPP）（与 IPP）的值与 IPP 和 DMAPP 相似；然而，两种类似物的 k（cat）值都明显较低。这些结果与亲电取代的解离机制一致，其中限速步骤从烯丙基底物中碳-氧键的异裂转变为同烯丙基底物中双键的烷基化。
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