Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility.
Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility.
复制标题
DOI：
10.1021/jo200482d
复制
发表时间：
2011-07-15
影响因子：
3.6
通讯作者：
Ly, Danith H.
中科院分区：
文献类型：
--
作者：
Sahu, Bichismita;Sacui, Iulia;Rapireddy, Srinivas;Zanotti, Kimberly J.;Bahal, Raman;Armitage, Bruce A.;Ly, Danith H.
在20世纪90年代早期开发的PNA由于其对DNA和RNA的强结合亲和力和序列选择性以及对蛋白酶和核酸酶的酶促降解的抗性而成为一类有前途的核酸模拟物;然而，与其他类别的寡核苷酸相比，其主要缺点是水溶性和生物相容性。在本文中，我们表明，在γ-骨架处安装相对小的亲水性（R）-二甘醇（“miniPEG”）单元将随机折叠的PNA转化为右手螺旋。本文报道了由市售的、相对便宜的Boc-L-丝氨酸经几步简单的反应合成光学纯的R-MPγPNA单体。一旦合成，R-MPγPNA寡聚体被预组织成右旋螺旋，并以更大的亲和力和序列选择性与DNA和RNA杂交，并且比亲本PNA寡聚体更具水溶性和更少聚集。本文提出的结果对PNA在生物学、生物技术和医学以及包括药物发现和分子工程在内的其他学科中的未来设计和应用具有重要意义。
Developed in the early 1990's, PNA has emerged as a promising class of nucleic acid mimic because of its strong binding affinity and sequence selectivity towards DNA and RNA, and resistance to enzymatic degradation by proteases and nucleases; however, the main drawbacks, as compared to other classes of oligonucleotides, are water solubility and biocompatibility. Herein we show that installation of a relatively small, hydrophilic (R)-diethylene glycol (`miniPEG') unit at the γ-backbone transforms a randomly-folded PNA into a right-handed helix. Synthesis of optically pure R-MPγPNA monomers is described, which can be accomplished in a few simple steps from a commercially available and relatively cheap Boc-L-serine. Once synthesized, R-MPγPNA oligomers are preorganized into a right-handed helix and hybridize to DNA and RNA with greater affinity and sequence selectivity, and are more water soluble and less aggregating than the parental PNA oligomers. The results presented herein have important implications for the future design and application of PNA in biology, biotechnology and medicine, as well as in other disciplines including drug discovery and molecular engineering.
登录
查看更多内容
DOI：
10.1002/cbic.200800441
发表时间：
2008-10-13
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15
作者：
Chakrabarti, R;Klibanov, AM
通讯作者：
Klibanov, AM
影响因子：
1.3
作者：
Bonora, Gian Maria;Drioli, Sara;Xodo, Luigi
通讯作者：
Xodo, Luigi
影响因子：
2.1
作者：
Debaene, Francois;Da Silva, Julien A.;Winssinger, Nicolas
通讯作者：
Winssinger, Nicolas
影响因子：
3.6
作者：
DUEHOLM, KL;EGHOLM, M;BUCHARDT, O
通讯作者：
BUCHARDT, O