Syntheses and biological activities of 12 N6-substituted adenosine 5'-phosphates and 15 cyclic 3',5'-phosphates are described. Included among these are the cyclic phosphates of the naturally occurring anticodon adjacent modified nucleosides, N6-(delta2-isopentenyl)adenosine and N-(purin-6-ylcarbamoyl)-L-threonine ribonucleoside. Also reported in this paper are the 5'-phosphates and cyclic phosphates of the cytokinins, N6-benzyladenosine, kinetin ribonucleoside, 3-(chloro-trans-2-buten-2-yl)adenosine,6-o-chlorophenylureidopurine ribonucleoside, and 6-allylureidopurine ribonucleoside. The 5'-nucleotides were prepared by direct phosphorylation of the corresponding ribonucleosides with POCl3 and triethyl phosphate. These compounds were converted to the cyclic 3',5'-phosphates by cyclization of the corresponding 5'-nucleotides with dicyclohexylcarbodiimide. Comparison of the cytotoxicity of the ribonucleosides with their 5'-nucleotides and cyclic 3',5'-nucleotides showed that some of the 5'-phosphates and cyclic phosphates were almost as active as the parent nucleosides. The 5'-nucleotides and the cyclic phosphates were more soluble than the parent nucleosides. The cyclic 3',5'-nucleotides were examined as alternate activators of cAMP-dependent protein kinase from beef heart. While all of the analogs studied showed some activity toward this enzyme, several compounds were more effective than cAMP itself. The analogs were also tested as substrates for cyclic 3',5'-nucleotide phosphodiesterase from beef heart. The N6-alkyl-cAMP analogs were poor substrates for the enzyme, while N6-carbamoyl-cAMP derivatives were inert toward this enzyme. These compounds did not inhibit the phosphodiesterase. Some of the cyclic phosphates exhibited marginal effect in the inhibition of glycogen synthesis in skin slices.

译文

描述了12种N6-substituted腺苷5 '-磷酸盐和15种环状3',5 '-磷酸盐的合成和生物活性。其中包括天然存在的反密码子邻近修饰核苷的环状磷酸盐,N6-(delta2-isopentenyl) 腺苷和N-(purin-6-ylcarbamoyl)-L-苏氨酸核糖核苷。本文还报道了细胞分裂素的5 '-磷酸盐和环状磷酸盐,N6-benzyladenosine激动素核糖核苷,3-(chloro-trans-2-buten-2-yl) 腺苷,6-o-氯苯基脲基嘌呤核糖核苷,和6-烯丙基脲基嘌呤核糖核苷。通过用POCl3和磷酸三乙酯直接磷酸化相应的核糖核苷制备5'-核苷酸。这些化合物被转化为环状3 ',5'-磷酸通过相应的5 '-核苷酸与二环己基碳二亚胺的环化反应。核糖核苷与其5'-核苷酸和环状3 '的细胞毒性比较,5'-核苷酸显示,一些5 '-磷酸盐和环状磷酸盐几乎和亲本核苷一样活跃。5'-核苷酸和环状磷酸盐比亲本核苷更易溶解。环状3 ',5'-核苷酸被检测为牛肉心脏cAMP依赖性蛋白激酶的替代激活剂。虽然所有研究的类似物都显示出对这种酶的一些活性,但几种化合物比cAMP本身更有效。类似物也被测试为环状3 '的底物,来自牛肉心脏的5'-核苷酸磷酸二酯酶。N6-alkyl-cAMP类似物是该酶的不良底物,而N6-carbamoyl-cAMP衍生物对该酶是惰性的。这些化合物不抑制磷酸二酯酶。一些环状磷酸盐在抑制皮肤切片中糖原合成方面表现出边际效应。

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