Synthesis of polyacrylamides N-substituted with PNA-like oligonucleotide mimics for molecular diagnostic applications

Two types of oligonucleotide mimics relative to peptide nucleic acids (PNAs ) were tested as probes in nucleic acid hybridisation assays based on polya crylamide technology. One type of mimic oligomers represented a chimera con structed of RNA and phosphono-PNA (pPNA) monomers, and the other one contai ned pPNA residues alternating with RNA-like monomers on the base of trans-4 -hydroxy-L-proline (HypNA). A chemistry providing efficient and specific co valent attachment of these DNA mimics to acrylamide polymers using a conven ient approach based on the co-polymerisation of acrylamide and some reactiv e acrylic acid derivatives with oligomers bearing 5'- or 3'-terminal acryla mide groups has been developed. A comparative study of polyacrylamide conju gates with oligonucleotides and mimic oligomers demonstrated the suitabilit y and high potential of PNA-pPNA and HypNA-pPNA chimeras as sequence-specif ic probes in capture and detection of target nucleic acid fragments to serv e current forms of DNA arrays.