Horwitz J P, Misra R S, Rozhin J, Neenan J P, Huo A, Godefroi V C, Philips K D, Chung H L, Butke G, Brooks S C
Biochim Biophys Acta. 1978 Aug 7;525(2):364-72. doi: 10.1016/0005-2744(78)90231-0.
Analogs of adenosine 3',5'-diphosphate are described which aid in the characterization of the inhibition of estrone sulfurylation by 3'-phosphoadenosine 5'-phosphosulfate as mediated by bovine adrenal estrogen sulfotransferase (3'-5'-phosphosulfate:estrone 3-sulphotransferase, EC 2.8.2.4). The facile conversion of ribonucleosides to 2',3'-cyclic phosphate 5'-phosphate in neat pyrophosphoryl chloride is utilized to provide a reliable route to the requisite intermediates for enzymatic regiospecific conversion to ribonucleoside 3',5'- and 2',5'-diphosphates. The importance of the 3'-phosphate ester to inhibition of estrone sulfurylation is confirmed by Ki measurements. Replacement of the 6-amino group by hydrogen or oxygen leads to considerable loss in affinity for the enzyme as does also dimethylation of the exocylic amino group. Alterations in the pyrimidine ring are not well tolerated by the sulfotransferase but modifications in the imidazole ring as in tubercidin (7 -deazaadenosine) and 8-bromoadenosine 3',5'-diphosphate lead to an enhanced affinity. The latter findings are discussed in terms of an hypothesis of stacking of the aromatic ring of the estrogen substrate and the purine moiety and its analogs.
描述了3',5'-二磷酸腺苷类似物，这些类似物有助于表征3'-磷酸腺苷5'-磷酸硫酸酯（由牛肾上腺雌激素磺基转移酶介导）对雌酮硫酸化的抑制作用（3'-5'-磷酸硫酸酯：雌酮3-磺基转移酶，EC 2.8.2.4）。利用在纯焦磷酰氯中将核糖核苷轻松转化为2',3'-环磷酸5'-磷酸酯，为酶促区域特异性转化为核糖核苷3',5'-和2',5'-二磷酸酯提供了可靠的途径，以获得所需的中间体。通过Ki测量证实了3'-磷酸酯对雌酮硫酸化抑制的重要性。用氢或氧取代6-氨基会导致对该酶的亲和力显著丧失，环外氨基的二甲基化也是如此。嘧啶环的改变不能被磺基转移酶很好地耐受，但像杀结核菌素（7-脱氮腺苷）和8-溴腺苷3',5'-二磷酸酯那样的咪唑环修饰会导致亲和力增强。根据雌激素底物的芳香环与嘌呤部分及其类似物的堆积假说对后一发现进行了讨论。
