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2-氮杂-1,N6-乙烯基三磷酸腺苷对哺乳动物聚腺苷酸聚合酶的抑制作用。

Inhibition of mammalian polyadenylate polymerase by 2-aza-1,N6-etheno-adenosine triphosphate.

作者信息

Keshgegian A A, Tsou K C, Furth J J

出版信息

Cancer Res. 1976 Sep;36(9 pt.1):3151-5.

PMID:989743
Abstract

2-Aza-1,N6-etheno-adenosine triphosphate (aza-epsilonATP), a fluorescent analog of adenosine triphosphate, significantly inhibits polyadenylate [poly(A)] polymerase of bovine lymphosarcoma and calf thymus, with 50% inhibition at 200 muM (in the presence of an equal concentration of adenosine triphosphate). Calf thymus RNA polymerases II and III are inhibited 32 and 20%, respectively, by a 3.8-fold excess of aza-epsilonATP; DNA polymerase alpha is not inhibited. The inhibition of poly(A) polymerase by aza-epsilonATP appears to be competitive with adenosine triphosphate; incorporation of aza-epsilonATP is not observed. Polymers of 2-aza 1,N6-etheno-adenosine monophosphate are used as primers, but pootly. 1,N-Etheno-adenosine triphosphate and 9-beta-D-arabinofuranosyladenine triphosphate are poor inhibitors of poly(A) polymerase; adenosine diphosphate is ineffective. Deoxyadenosine triphosphate inhibits to the same extent as aza-epsilonATP, while other naturally occurring nucleotides inhibit poly(A) polymerase to varying degrees, with deoxynucleoside triphosphates more potent than ribonucleoside triphosphates. Inhibition of poly(A) polymerase by naturally occurring nucleoside triphosphates suggests that nucleotides may regulate the enzyme in vivo; inhibition by the fluorescent analog aza-epsilonATP suggests that this compound may be useful in elucidating poly(A) metabolism in both normal and neoplastic cells.

摘要

2-氮杂-1,N6-乙撑腺苷三磷酸(氮杂-ε-ATP),一种腺苷三磷酸的荧光类似物,能显著抑制牛淋巴肉瘤和小牛胸腺的聚腺苷酸[poly(A)]聚合酶,在200μM时抑制率达50%(在存在等浓度腺苷三磷酸的情况下)。小牛胸腺RNA聚合酶II和III分别被3.8倍过量的氮杂-ε-ATP抑制32%和20%;DNA聚合酶α未被抑制。氮杂-ε-ATP对聚(A)聚合酶的抑制作用似乎与腺苷三磷酸具有竞争性;未观察到氮杂-ε-ATP的掺入。2-氮杂1,N6-乙撑腺苷单磷酸的聚合物用作引物,但效果不佳。1,N-乙撑腺苷三磷酸和9-β-D-阿拉伯呋喃糖基腺嘌呤三磷酸是聚(A)聚合酶的弱抑制剂;二磷酸腺苷无效。脱氧腺苷三磷酸的抑制程度与氮杂-ε-ATP相同,而其他天然存在的核苷酸对聚(A)聚合酶有不同程度的抑制作用,脱氧核苷三磷酸比核糖核苷三磷酸更有效。天然存在的核苷三磷酸对聚(A)聚合酶的抑制作用表明核苷酸可能在体内调节该酶;荧光类似物氮杂-ε-ATP的抑制作用表明该化合物可能有助于阐明正常细胞和肿瘤细胞中的聚(A)代谢。

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