Conformationally restricted cationic polyamide analogs of nucleic acids: Design, synthesis, and DNA/RNA binding studies
V. A. Kumar, M. D'Costa, P. S. Lonkar, Meena, P. S. Pallan, and K. N. Ganesh
Division of Organic Chemistry (Synthesis), National
Chemical Laboratory, Pune 411008, India
Abstract: The remarkable medicinal importance of the achiral,
acyclic, and uncharged aminoethylglycyl peptide nucleic acids (aegPNAs)
as DNA/RNA mimics has challenged chemists to circumvent the limitations
of their in vivo efficacy. In this context, we have designed conformationally
restricted five- and six-membered cyclic PNA analogs by introduction
of chemical bridges in aegPNAs leading to a large variety of
structures with defined configurations and conformational preferences,
effecting concomitant installation of a positive charge in the backbone.
The synthesis and biophysical properties of these cationic aminoethylprolyl
PNAs, pyrrolidine PNAs, and piperidine PNAs endowed with
increased water solubility and affinity toward target nucleic acids
is presented. These nucleic acid analogs as lead structures are a part
of a chemical evolution process that might give rise to a synthetic
nucleic acid analog having optimum properties for medicinal applications.
*Lecture presented at the symposium "Chemistry of nucleic acids", as part of the 39th IUPAC Congress and 86th Conference of the Canadian Society for Chemistry: Chemistry at the Interfaces, Ottawa, Canada, 10-15 August 2003. Other Congress presentations are published in this issue, pp. 1295-1603.
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