A new class of biopolymers has been developed that combine the molecular recognition properties of DNA and RNA with expanded functionality and chemical diversity. As in nucleic acids, complementary' strands of the biopolymer recognize each other by Watson-Crick base pairing rules. Further, we have shown that these biopolymers can be replicated in a variety of template-directed biopolymerization reactions using DNA and RNA polymerases. The daughter molecules can themselves encode daughter, molecules. and it should be possible to explore molecular diversity with these molecules via a process of mutation and selection. Unlike DNA and RNA, however. these biopolymers are built from 12 building blocks rather than only 4. Several of these building blocks carry functional groups which provide the biopolymer with much of tile structural versatility of more complex molecules such as proteins. The goal of this project is to establish the feasibility of using DNA and RNA polymerases, previously identified in preliminary, to amplify the biopolymer by a polymerase chain reaction-type process. The commercial products sought are oligonucleotides that are ligands for biological receptors, receptors for biological ligands and amplifiable tags for diagnostic assays that do not cross react with naturally-occurring nucleic acids.
The commercial applications for novel base pairs and oligonucleotide analogs in which they are contained include drug discovery and diagnostics. Through the creation of molecular diversity, libraries of oligonucleotide analogs with expanded chemical functionality can be created for screening as ligands against target receptors. In the diagnostic area, molecular tags or handles are desired that do not cross-react with naturally-occurring oligonucleotides, but which can form base pairs with a complementary novel base.
| Sherrill, Christopher B; Marshall, David J; Moser, Michael J et al. (2004) Nucleic acid analysis using an expanded genetic alphabet to quench fluorescence. J Am Chem Soc 126:4550-6 |
