Chiral Peptide Nucleic Acids - Isis Project No 66
Peptide Nucleic Acids for Therapeutics and Diagnostics.
Background
Oligonucleotides are potentially useful for the regulation of genetic expression by binding with DNA and RNA. Since natural oligonucleotides are degraded by nucleases, there has been considerable interest in synthetic oligonucleotide analogues that are stable in physiological conditions.
Problem with Existing Peptide Nucleic Acids
The sugar phosphate backbone of a nucleic acid consists of a repeating unit of six atoms, configuratively and conformationally constrained by the D-ribose or 2'-deoxy-D-ribose ring. Researchers at Oxford have been investigating its replacement by dipeptide unit, so that the new backbone is amenable to preparation by solid phase peptide synthesis. The dipeptide unit compromises a "nucleo amino acid" derived from proline and a "spacer amino acid" which can be any amino acid chosen to provide desired properties.
The Oxford Invention
By using suitable protecting groups, dipeptide analogues of the four standard nucleotides have been prepared. A solid phase technique has been used to convert these nucleotide analogues into peptide analogues of oligonucleotides with both single and mixed base sequences. There is much scope for variation of the "spacer amino acids". Changes can be made to the chiral PNA's hydrophobicity to assist cell penetration or its charge to increase its interaction with DNA. Such molecules are of interest in the diagnosis of genetic disorders, in the identification of gene function from sequence, and as therapeutic anti sense agents against tumours and viruses.
Commercialisation
This work forms the basis of a patent application assigned to Isis Innovation for exploitation by the commercial world. Companies interested in exploiting the technology should contact Isis for further details.