Noonan T, Brown N, Dudycz L, Wright G
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
J Med Chem. 1991 Apr;34(4):1302-7. doi: 10.1021/jm00108a010.
A series of N2-substituted guanosine 5'-triphosphates was synthesized from the corresponding nucleosides. The nucleosides were prepared by treatment of N2-substituted guanines with tetra-O-acetylribose under conditions which maximized the yield of the 9-beta-guanosine isomers. These nucleotides and several sugar- and base-modified analogues of GTP were tested for their ability to bind to cellular and oncogenic forms of the GTP/GDP binding proteins, Ha-ras-p21. Several N2-substituted GTPs showed affinities higher than that of GDP itself, and the N2-[p-(n-butyl)phenyl] derivative bound to the oncogenic mutant, Leu-61 p21, twice as strongly as to the cellular protein. Changes in relative affinities of the nucleotides are discussed with reference to reported crystallographic structures of p21.
一系列 N2-取代的鸟苷 5'-三磷酸由相应的核苷合成。核苷是通过在使 9-β-鸟苷异构体产率最大化的条件下，用四-O-乙酰核糖处理 N2-取代的鸟嘌呤来制备的。测试了这些核苷酸以及几种 GTP 的糖基和碱基修饰类似物与 GTP/GDP 结合蛋白 Ha-ras-p21 的细胞形式和致癌形式结合的能力。几种 N2-取代的 GTP 显示出比 GDP 本身更高的亲和力，并且 N2-[对-(正丁基)苯基]衍生物与致癌突变体 Leu-61 p21 的结合强度是与细胞蛋白结合强度的两倍。参考已报道的 p21 晶体结构讨论了核苷酸相对亲和力的变化。
