Wei Z, Tung C H, Zhu T, Dickerhof W A, Breslauer K J, Georgopoulos D E, Leibowitz M J, Stein S
Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
Nucleic Acids Res. 1996 Feb 15;24(4):655-61. doi: 10.1093/nar/24.4.655.
The hybridization properties of a series of probes, based on two 9mer oligodeoxynucleotides (designated as I and II) having an appended oligoarginine chain (Rn) to produce peptide-oligonucleotide conjugates or peptide-bridged oligonucleotide pairs (e.g. Rn-I or II-Rn-I), were investigated. For the double-linked probes, we found that the peptide bridge induces the two 9mers to bind complementary single-stranded DNA or RNA targets with substantially enhanced thermal stability. The resulting hybrid with complementary DNA was found to assume a 1:1 complex in the B conformation as judged by UV mixing curves and CD spectroscopy. Complexes of single or double-linked probes with complementary RNA exhibited sensitivity to RNase H digestion. The influence of the identity and chirality of the repeating unit in the bridge, the length of the bridge, the gap size and the salt concentration on the hybridization properties of this new class of oligonucleotide probes was also studied. Our data reveal that these compounds exhibit properties that should prove useful in the development of antisense strategies.
研究了一系列基于两个9聚体寡脱氧核苷酸（分别命名为I和II）的探针的杂交特性，这些寡脱氧核苷酸连接有寡聚精氨酸链（Rn）以生成肽 - 寡核苷酸缀合物或肽桥接寡核苷酸对（例如Rn - I或II - Rn - I）。对于双链探针，我们发现肽桥可诱导两个9聚体与互补的单链DNA或RNA靶标结合，且热稳定性显著增强。通过紫外混合曲线和圆二色光谱判断，所得与互补DNA的杂交体呈现B构象的1:1复合物。单链或双链探针与互补RNA的复合物对RNase H消化敏感。还研究了桥中重复单元的同一性和手性、桥的长度、间隙大小和盐浓度对这类新型寡核苷酸探针杂交特性的影响。我们的数据表明，这些化合物展现出的特性在反义策略开发中应会很有用。
