Synthetic studies on peptide nucleic acids: 1. Toward a circular bis-peptide nucleic acid. 2. Sequence and linker effects in bis-PNA hybridization to DNA.

摘要

The PNA monomers of thymine and cytosine were synthesized and incorporated into a series of hairpin bis-PNA ligands by solid phase peptide synthesis using the Boc/Cbz protecting group strategy. The identity of the ligands were confirmed by MALDI-TOF mass spectrometry. Using these ligands, sequence dependent effects on PNA2/DNA triple helix stability were studied by means of thermal denaturation profiles. Furthermore, a novel linker based on the aminoethylglycine backbone unit was employed in this study and it has been found that under acidic conditions, this linker can enhance significantly the stability of PNA2/DNA triple helices.;In an effort to develop new synthetic routes to novel PNA monomers and oligomers, an on-resin Sonogashira cross coupling reaction between propargyl alcohol and a PNA oligomer containing 5'-iodouracil is described. Characterization of this oligomer was performed using MALDI-TOF mass spectrometry.;Finally, progress towards the synthesis of a circular bis -PNA ligand using a templated chemical ligation reaction is reported.