Jennings Benjamin C, Danowitz Amy M, Wang Yen-Chih, Gibbs Richard A, Distefano Mark D, Fierke Carol A
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Chemistry and Biochemistry, Mercyhurst University, Erie, PA 16546, USA.
Bioorg Med Chem Lett. 2016 Feb 15;26(4):1333-6. doi: 10.1016/j.bmcl.2015.12.079. Epub 2015 Dec 22.
Attempts to identify the prenyl-proteome of cells or changes in prenylation following drug treatment have used 'clickable' alkyne-modified analogs of the lipid substrates farnesyl- and geranylgeranyl-diphosphate (FPP and GGPP). We characterized the reactivity of four alkyne-containing analogs of FPP with purified protein farnesyltransferase and a small library of dansylated peptides using an in vitro continuous spectrofluorimetric assay. These analogs alter prenylation specificity and reactivity suggesting that in vivo results obtained using these FPP analogs should be interpreted cautiously.
试图鉴定细胞的异戊二烯化蛋白质组或药物处理后异戊二烯化的变化，使用了脂质底物法尼基二磷酸和香叶基香叶基二磷酸（FPP和GGPP）的“可点击”炔烃修饰类似物。我们使用体外连续荧光分光光度法，对四种含炔烃的FPP类似物与纯化的蛋白质法尼基转移酶以及一个丹磺酰化肽小文库的反应活性进行了表征。这些类似物改变了异戊二烯化特异性和反应活性，这表明使用这些FPP类似物获得的体内结果应谨慎解读。
