In vitro stability of α-Helical peptide nucleic acids (αPNAs)

α-Helical peptide nucleic acids (αPNAs) are synthetic molecules that merge the α-helix secondary structure of peptides with the codified Watson–Crick base pairing capability of nucleic acids. It is now demonstrated that αPNAs made up of either - or -amino acids are resistant to degradation by the proteases present in human serum. The increased stability of αPNAs towards proteases may be attributable to the presence of unnatural nucleoamino acid residues [–NHCH(CH2OCH2B)CO–, where B=thymine or cytosine] since the replacement of these amino acids by serine yields a control peptide that does break down in human serum. The stability of αPNAs towards proteases makes them attractive candidates for further development as antisense agents.