SYNTHESIS AND EVALUATION OF SOME PROPERTIES OF CHIMERIC OLIGOMERS CONTAINING PNA AND PHOSPHONO-PNA RESIDUES

In an attempt to improve physico-chemical and biological properties of peptide nucleic acids (PNAs), particularly water solubility and cellu lar uptake, the synthesis of chimeric oligomers consisted of PNA and p hosphono-PNA analogues (pPNAs) bearing the four natural nucleobases ha s been accomplished. Sb produce these chimeras, pPNA monomers of two t ypes containing N-(2-hydroxyethyl)phasphonoglycine, or N-(2-aminoethyl )phosphonoglycine backbone, were used in conjunction with PNA monomers representing derivatives of N-(2-aminoethyl)glycine, or N-(2-hydroxye thyl)glycine. The oligomers obtained were composed of either PNA and p PNA stretches or alternating PNA and pPNA monomers. The examination of hybridization properties of PNA-pPNA chimeras to DNA and RNA compleme ntary strands in comparison with pure PNAs, acid pPNAs as well as DNA- pPNA hybrids and DNA fragments confirmed that these chimeras farm stab le complexes with complementary DNA and RNA fragments, They were found to be resistant to degradation by nucleases. All these properties tog ether with good solubility in water make PNA-pPNA hybrids promising fo r further evaluation as potential therapeutic agents.