Gangamani B P, Kumar V A, Ganesh K N
Organic Chemistry Synthesis Division, National Chemical Laboratory, Pune, India. f1p4
Biochem Biophys Res Commun. 1997 Nov 26;240(3):778-82. doi: 10.1006/bbrc.1997.7745.
Peptide Nucleic Acids (PNAs), the achiral DNA mimics with amide backbone, are emerging as attractive leads for drug development by antisense approach. Two major limitations of PNAs from an application perspective are their limited solubility in aqueous systems and pronounced self-organization. In this paper, it is shown that covalent conjugation of spermine at C-terminus of PNA (spPNA) improves its solubility and binds to complementary DNA 20 times stronger than the corresponding binding of PNA. Fluorescence kinetics shows a 2 fold acceleration of the bimolecular association process in spPNA:DNA hybrids, due to electrostatic interaction cationic spermine tagged to PNA with anionic DNA. This modification is easy to incorporate into PNA synthetic protocols to make them more effective in biological applications and may improve the poor cell uptake of PNA.
肽核酸（PNA）是一种具有酰胺主链的非手性DNA模拟物，正作为反义方法药物开发的有吸引力的先导物而崭露头角。从应用角度来看，PNA的两个主要局限性是其在水性体系中的溶解度有限以及明显的自组装现象。本文表明，在PNA的C末端共价连接精胺（spPNA）可提高其溶解度，并且与互补DNA的结合力比相应的PNA结合强20倍。荧光动力学表明，由于带正电的精胺与带负电的DNA之间的静电相互作用，spPNA:DNA杂交体中的双分子缔合过程加速了2倍。这种修饰易于纳入PNA合成方案，使其在生物应用中更有效，并且可能改善PNA较差的细胞摄取情况。
