9-β-D-呋喃木糖基腺嘌呤的2'-5'-连接三聚体抑制疱疹病毒生长的机制

Mechanism of inhibition of herpesvirus growth by 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine.

作者信息

Goswami B B, Gosselin G, Imbach J L, Sharma O K

出版信息

Virology. 1984 Sep;137(2):400-7. doi: 10.1016/0042-6822(84)90232-0.

Abstract

The 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine (XyloA)3 is an extremely potent inhibitor of growth of herpes simplex viruses 1 and 2. Evidence is presented that in spite of its increased stability in cell-free extracts (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982), intact (XyloA)3 was not detected in Vero cells, but instead was rapidly degraded in the medium to monomeric 9-beta-D-xylofuranosyladenine (XyloA). The XyloA thus formed was rapidly taken up by cells, phosphorylated to its triphosphate, and produced inhibition of RNA synthesis. The observed inhibition of DNA synthesis (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982) and herpesvirus growth by (XyloA)3 (D.A. Eppstein, J.W. Barnett, Y.V. Marsh, G. Gosselin, and J.L. Imbach, Nature (London) 302, 723, 724, 1983) is most likely the result of inhibition of RNA synthesis by its degradation product XyloA.

摘要

9-β-D-木糖呋喃糖基腺嘌呤（XyloA）的2'-5'-连接三聚体（XyloA）3是单纯疱疹病毒1型和2型生长的极强抑制剂。有证据表明，尽管（XyloA）3在无细胞提取物中稳定性增加（D.A.埃普斯坦、Y.V.马什、B.B.施赖弗、M.A.拉森、J.W.巴尼特、J.P.H.费尔海登和E.J.普里斯贝，《生物化学杂志》257，13390 - 13397，1982），但在Vero细胞中未检测到完整的（XyloA）3，而是在培养基中迅速降解为单体9-β-D-木糖呋喃糖基腺嘌呤（XyloA）。如此形成的XyloA被细胞迅速摄取，磷酸化为其三磷酸盐，并抑制RNA合成。观察到的DNA合成抑制（D.A.埃普斯坦、Y.V.马什、B.B.施赖弗、M.A.拉森、J.W.巴尼特、J.P.H.费尔海登和E.J.普里斯贝，《生物化学杂志》257，13390 - 13397，1982）以及（XyloA）3对疱疹病毒生长的抑制（D.A.埃普斯坦、J.W.巴尼特、Y.V.马什、G.戈斯林和J.L.安巴赫，《自然》（伦敦）302，723，724，1983）很可能是其降解产物XyloA抑制RNA合成的结果。