Synthesis and DNA-recognition behavior of a novel peptide ribonucleic acid with a serine backbone (oxa-PRNA)
Synthesis and DNA-recognition behavior of a novel peptide ribonucleic acid with a serine backbone (oxa-PRNA)
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DOI：
10.1016/j.tet.2009.10.094
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发表时间：
2010-01-02
期刊：
影响因子：
2.1
通讯作者：
Inoue, Yoshihisa
中科院分区：
文献类型：
--
作者：
Sawa, Nobuya;Wada, Takehiko;Inoue, Yoshihisa
以L-丝氨酸为单体合成了(2S)-2-Fmoc-amino-3-(5‘-deoxyuridinylamino)-3-oxopropyloxyacetic酸，用于制备含氧基肽骨架的第二代多肽核糖核酸。引入了醚键来改善具有异谷氨酰胺主链的原始PRNA在水溶液中的适度溶解性，而不会损害氨基尿苷侧链通过加入硼砂而改变反/同步核苷酸碱基取向的能力。的确，圆二色谱分析表明，分三步合成的Fmoc保护的oxa-PRNA尿苷单体(Fmoc-oxa-PRNA(U))在磷酸缓冲液中加入硼砂后，碱基取向从反向转变为同步。采用Fmoc固相合成法，以适中的产率合成了带有和不带有Arg端帽的oxa-PRNA(U)HOMO-12聚体。所合成的N-末端和C-末端封端的oxa-PRNA(U)12聚体均能与互补DNA 12聚体(d(A(12))杂交，其稳定性与天然配对相当。(C)2009爱思唯尔有限公司。保留所有权利。
(2S)-2-Fmoc-amino-3-(5'-deoxyuridinylamino)-3-oxopropyloxyacetic acid was synthesized from L-serine as a monomer for preparing the second-generation peptide ribonucleic acid with an oxa-peptide backbone (oxa-PRNA). The ether linkage was incorporated to improve the modest solubility in aqueous solution of the original PRNA with an iso-glutamine backbone, without harming the ability of the aminouridine side chain to switch the anti/syn nucleobase orientation by adding borax. Indeed, CD spectral examinations revealed that the Fmoc-protected oxa-PRNA uridine monomer (Fmoc-oxa-PRNA(U)), synthesized in three steps, switched the nucleobase orientation from anti to syn in phosphate buffer upon addition of borax. Homo-12mers of oxa-PRNA(U) with and without Arg end caps were prepared in moderate yields by the Fmoc solid-phase synthesis. Both of the N- and C-terminus-capped oxa-PRNA(U) 12mers thus synthesized were shown to hybridize with the complementary DNA 12mer (d(A(12))) with stabilities comparable to that observed for the natural pair. (C) 2009 Elsevier Ltd. All rights reserved.