Aminomethylene peptide nucleic acid (am-PNA): synthesis, regio-/stereospecific DNA binding, and differential cell uptake of (α/γ,R/S)am-PNA analogues.
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.
Organic Chemistry Division, National Chemical Laboratory, Pune 411008, India.
Roopa
R
Mitra
Krishna N
KN
Ganesh
D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D018076:DNA, Complementary / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D018076:DNA, Complementary; D020135:Peptide Nucleic Acids