Inhibition of adenylate kinase by P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate and P1-(lin-benzo-5'-adenosyl)-P5-(5'-adenosyl pentaphosphate.
Inhibition of adenylate kinase by P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate and P1-(lin-benzo-5'-adenosyl)-P5-(5'-adenosyl pentaphosphate.
复制标题
P1-(lin-苯并-5-腺苷)-P4-(5-腺苷)四磷酸和P1-(lin-苯并-5-腺苷)-P5-(5-腺苷五磷酸)抑制腺苷酸激酶。
作者：
P. Vanderlijn;J. Barrio;N. Leonard
以邻苯并腺苷5 ′-单磷酸吗啉酯、腺苷5 ′-四磷酸和腺苷5 ′-三磷酸为原料，合成了β 1-（邻苯并腺苷）-β 5-（5 ′-腺苷）五磷酸和β 1-（邻苯并腺苷）-β 4-（5 ′-腺苷）四磷酸。这些混合的二核苷多磷酸是猪肌肉腺苷酸激酶的有效抑制剂，通过动力学和荧光实验测定，五磷酸和四磷酸的缔合常数分别为2 × 10（5）M-1和2 × 10（6）M-1。这两种抑制剂结合腺苷酸激酶后的荧光强度和荧光寿命的增加是由于当这些配体在溶液中游离时观察到的分子内堆积相互作用的破坏，并暗示它们以“开放”或“扩展”形式与酶结合。这些结果和这些抑制剂的尺寸要求进行了讨论，我们目前的知识腺苷酸激酶的活性位点和已知的腺苷酸激酶抑制剂，P1，P5-双（5 '-腺苷）五磷酸和P1，P4-双-（5'-腺苷）四磷酸。
P1-(lin-Benzo-5'-adenosyl)-P5-(5'-adenosyl) penraphosphate and P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate have been synthesized from lin-benzoadenosine 5'-monophosphoromorpholidate and adenosine 5'-tetraphosphate and adenosine 5'-triphosphate. These mixed dinucleoside polyphosphates are potent inhibitors of porcine muscle adenylate kinase, with association constants of 2 x 10(5) M-1 for the pentaphosphate and 2 x 10(6) M-1 for the tetraphosphate, respectively, as determined by kinetics and fluorescence experiments. The increase in fluorescence intensities and fluorescence lifetimes of both inhibitors upon binding to adenylate kinase results from a breaking of the intramolecular stacking interaction observed when these ligands are free in solution and implicates their binding to the enzyme in an "open" or "extended" form. These results and the dimensional requirements of these inhibitors are discussed in relation to our current knowledge of the active site of adenylate kinase and to the known inhibitors of adenylate kinase, P1,P5-bis(5'-adenosyl) pentaphosphate and P1,P4-bis-(5'-adenosyl) tetraphosphate.