Organic Chemistry Division, National Chemical Laboratory, Pune 411008, India.
J Org Chem. 2012 Jul 6;77(13):5696-704. doi: 10.1021/jo300860f. Epub 2012 Jun 19.
Inherently chiral, cationic am-PNAs having pendant aminomethylene groups at α(R/S) or γ(S) sites on PNA backbone have been synthesized. The modified PNAs are shown to stabilize duplexes with complementary cDNA in a regio- and stereo-preferred manner with γ(S)-am PNA superior to α(R/S)-am PNAs and α(R)-am PNA better than the α(S) isomer. The enhanced stabilization of am-PNA:DNA duplexes is accompanied by a greater discrimination of mismatched bases. This seems to be a combined result of both electrostatic interactions and conformational preorganization of backbone favoring the cDNA binding. The am-PNAs are demonstrated to effectively traverse the cell membrane, localize in the nucleus of HeLa cells, and exhibit low toxicity to cells.
具有手性中心的阳离子型酰胺键修饰的肽核酸（am-PNAs），其酰胺基甲基侧链分别位于 PNA 主链的α（R/S）或γ（S）位。这些修饰的 PNAs 以区域和立体选择性的方式稳定与互补 cDNA 的双链，其中γ（S）-酰胺键修饰的 PNA 优于α（R/S）-酰胺键修饰的 PNA，而α（R）-酰胺键修饰的 PNA 又优于其α（S）异构体。酰胺键修饰的 PNA 与 DNA 双链的稳定性增强伴随着对错配碱基的更高识别。这似乎是静电相互作用和有利于 cDNA 结合的主链构象预组织的综合结果。实验证明，酰胺键修饰的 PNAs 能够有效地穿过细胞膜，定位于 HeLa 细胞的核内，并且对细胞的毒性较低。
