Severin E S, Nesterova M V, Sashchenko L P, Rasumova V V
Biochim Biophys Acta. 1975 Apr 19;384(2):413-22. doi: 10.1016/0005-2744(75)90042-x.
2'-O-Chloroacetyl cyclic AMP, 2'-O-acrylyl cyclic AMP and N-6, 2'-O-diacrylyl cyclic AMP were synthesized by the reaction of cyclic AMP with chloroacetic and acrylic anhydrides, respectively. Selective O-deacylation of N-6, 2'-O-diacrylyl cyclic AMP yielded N-6 -monoacrylyl cyclic AMP. In the reaction of gamma-mercaptobutyric acid with 8-bromo cyclic AMP, 8-(gamma-carboxypropylthio) cyclic AMP was obtained. The compounds synthesized and other cyclic AMP analogues (8-bromo cyclic AMP and adenosine 3', 5'-cyclic sulphate) were tested for ability to interact with the highly purified pig brain histone kinase. All compounds under study were found to be activators of the enzyme. The highest activating potency was manifested by 8-bromo cyclic AMP and 8-(gamma-carboxypropylthio) cyclic AMP; adenosine 3', 5'-cyclic sulphate was the least potent in this respect. All compounds were shown to inhibit binding of cyclic [-3-H]AMP to histone kinase. The inhibition was competitive with respect to cyclic AMP in all cases. All compounds, except for 2'-O-chloroacetyl cyclic AMP may indicate the formation of a covalent bond between this analogue and the enzyme. These findings suggest that an active site of the regulatory subunit of the histone kinase contains at least three specific areas responsible for cyclic AMP binding.
分别通过环磷酸腺苷（cAMP）与氯乙酸酐和丙烯酸酐的反应合成了2'-O-氯乙酰基环磷酸腺苷、2'-O-丙烯酰基环磷酸腺苷和N-6,2'-O-二丙烯酰基环磷酸腺苷。N-6,2'-O-二丙烯酰基环磷酸腺苷的选择性O-脱酰基反应生成了N-6-单丙烯酰基环磷酸腺苷。在γ-巯基丁酸与8-溴环磷酸腺苷的反应中，得到了8-(γ-羧丙基硫基)环磷酸腺苷。对合成的化合物以及其他环磷酸腺苷类似物（8-溴环磷酸腺苷和腺苷3',5'-环硫酸盐）进行了与高度纯化的猪脑组蛋白激酶相互作用能力的测试。发现所有研究的化合物都是该酶的激活剂。8-溴环磷酸腺苷和8-(γ-羧丙基硫基)环磷酸腺苷表现出最高的激活效力；腺苷3',5'-环硫酸盐在这方面效力最低。所有化合物均显示抑制环[-3-H]AMP与组蛋白激酶的结合。在所有情况下，这种抑制作用对环磷酸腺苷而言都是竞争性的。除2'-O-氯乙酰基环磷酸腺苷外，所有化合物可能表明该类似物与酶之间形成了共价键。这些发现表明，组蛋白激酶调节亚基的活性位点至少包含三个负责环磷酸腺苷结合的特定区域。
