Chimeric peptide nucleic acids incorporating (2S, 5R)-aminoethyl pipecolyl units: synthesis and DNA binding studies

Abstract

The design and facile synthesis of a novel chiral six-membered PNA analogue (2S,5R)-1-(N-Boc-aminoethyl)-5-(thymin-1-yl)pipecolic acid, aepipPNA, that upon incorporation into PNA sequences effected stabilization of complexes with target complementary DNA. This is the first example where a six membered-PNA is shown to be capable of forming stable complexes with DNA and further expands the repertoire of cyclic PNA analogues. The six-membered pipecolic acid based aepipPNA is a higher homologue of aminoethylprolyl PNA. The synthesis of the thyminyl-2S,5R-aepipPNA monomer is reported. The preliminary results of the synthesis, characterization, and DNA binding properties of the triplex forming chimeric aegPNA-aepipPNA oligomers are described.