Synthesis and Enzymatic Studies of Isoprenoid Thiolo Bisubstrate Analogues

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• 作者：Gurusankar Ramamoorthy ; Richard M. Phan ; C. Dale Poulter
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：June 17, 2016
• 年：2016
• 卷：81
• 期：12
• 页码：5093-5100
• 全文大小：411K
• 年卷期：0
• ISSN：1520-6904

文摘

Chain elongation prenyltransferases catalyze the addition of the hydrocarbon moiety of allylic isoprenoid diphosphates to the carbon–carbon double bond in isopentenyl diphosphate (IPP) in the primary building reactions in the isoprenoid biosynthetic pathway. Bis-O-diphosphate analogues 3-OPP/OPP, 4-OPP/OPP, and 5-OPP/OPP and bis-thiolodiphosphate bisubstrate analogues 3-SPP/SPP, 4-SPP/SPP, and 5-SPP/SPP were synthesized. The analogues 4-OPP/OPP, 5-OPP/OPP, 4-SPP/SPP, and 5-SPP/SPP were excellent competitive inhibitors of avian farnesyl diphosphate synthase with K_I = 1.0 ± 0.12 μM, K_I = 0.5 ± 0.2 μM, K_I = 0.7 ± 0.3 μM, and K_I = 2.9 ± 0.27 μM, respectively, whereas, analogues 3-OPP/OPP and 3-SPP/SPP displayed mixed type inhibition with K_I = 1.4 μM and K_I = 5.5 μM, respectively.