Chemical synthesis of diastereomeric diadenosine boranophosphates (ApbA) from 2′-O-(2-cyanoethoxymethyl)adenosine by the boranophosphotriester method

被引：14

作者：

Enya, Yukiko ^{[1
]}

Nagata, Seigo ^{[1
]}

Masutomi, Yutaka ^{[2
]}

Kitagawa, Hidetoshi ^{[1
]}

Takagaki, Kazuchika ^{[1
]}

Oka, Natsuhisa ^{[3
]}

Wada, Takeshi ^{[3
]}

Ohgi, Tadaaki ^{[1
]}

Yano, Junichi ^{[2
]}

机构：

[1] Nippon Shinyaku Co Ltd, Discovery Res Labs, Tsukuba, Ibaraki 3050003, Japan

[2] Nippon Shinyaku Co Ltd, Discovery Res Labs, Minami Ku, Kyoto 6018550, Japan

[3] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 20期

关键词：

boranophosphate; diadenosine; poly(U); 2-cyanoethoxymethyl; nuclease resistance; T(m) value;

D O I：

10.1016/j.bmc.2008.09.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have synthesized diastereomerically pure diadenosine 3 ',5 '-boranophosphates (Ap(b)A) by using the boranophosphotriester method from ribonucleosides protected with the 2 '-hydroxy protecting group 2-cyanoethoxymethyl (CEM). Melting curves of the triple-helical complex of the dimer ApbA and 2poly(U) at high ionic strength revealed that presumptive (Sp)-Ap(b)A had a much higher affinity and presumptive (Rp)-Ap(b)A a much lower affinity for poly(U) than the natural dimer ApA did. In contrast, the affinities of these dimers for poly(dT) were similar. Both the (Rp)- and the (Sp)-boranophosphate diastereomers showed much higher resistance to digestion by snake venom phosphodiesterase and nuclease P1 than ApA did. They have potential for use as synthons to be incorporated into boranophosphate oligonucleotides. In particular, because oligonucleotides containing Sp boranophosphate nucleotides are expected to bind more strongly and specifically to RNA than natural oligoribonucleotides do, they may find application in the isolation and detection of functional RNA in basic research and diagnostics. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：9154 / 9160

页数：7

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