PEPTIDE NUCLEIC-ACIDS AND THEIR PHOSPHONATE ANALOGS - SYNTHESIS AND HYBRIDIZATION PROPERTIES

The synthesis of a series of DNA mimics-peptide nucleic acids, phospho nate analogues of peptide nucleic acids, and their hybrids-is describe d. The preparative synthesis of the corresponding monomers and the sol id phase automated synthesis of oligomers-mimics are developed. Modifi ed phosphonate analogues of peptide nucleic acids, in particular chira l derivatives and those with additional hydroxyl groups in the side ch ains of the backbone as well as pyrene derivatives of peptide nucleic acids and their phosphonate analogues, are prepared. The ability of th e resulting oligomers specifically to hybridize to DNA and RNA complem entary chains is studied. It is shown that phosphonate analogues of pe ptide nucleic acids and their hybrids with peptide nucleic acids can f orm complexes with the DNA and RNA complementary strands, the stabilit y of the complexes increasing in parallel with the increase in the num ber of peptide nucleic acid residues in the chain of the mimic. This p roperty, along with good water solubility, provides the precondition f or further evaluation of these compounds as antisense and antigene age nts.