Oligonucleotide analogs with peptide internucleotide linkages.

Oligonucleotide analogs containing one or a few glycine, L-, and D-alanine or L-and D-phenylalanine residues instead of phosphodiesterinternucleotide linkages were synthesized. The stability of the duplexes formed by modified oligonucleotides and their wildtype complements was studied. Oligonucleotides with D-alanine residues in internucleotide linkages form duplexes more stable than native ones (ΔT(m) +0.2 °C per modification), whereas other modifications destabilize the duplexes.