title: An in vitro translation, selection and amplification system for peptide nucleic acids.
abstract: Methods to evolve synthetic, rather than biological, polymers could significantly expand the functional potential of polymers that emerge from in vitro evolution. Requirements for synthetic polymer evolution include (i) sequence-specific polymerization of synthetic building blocks on an amplifiable template, (ii) display of the newly translated polymer strand in a manner that allows it to adopt folded structures, (iii) selection of synthetic polymer libraries for desired binding or catalytic properties and (iv) amplification of template sequences that survive selection in a manner that allows subsequent translation. Here we report the development of such a system for peptide nucleic acids (PNAs) using a set of 12 PNA pentamer building blocks. We validated the system by performing six iterated cycles of translation, selection and amplification on a library of 4.3 x 10(8) PNA-encoding DNA templates and observed >1,000,000-fold overall enrichment of a template encoding a biotinylated (streptavidin-binding) PNA. These results collectively provide an experimental foundation for PNA evolution in the laboratory.
authors.affiliation: Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Brudno
authors.forename: Michael E
authors.initials: ME
authors.lastname: Birnbaum
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Kleiner
authors.forename: David R
authors.initials: DR
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D030561:Databases, Nucleic Acid; D005815:Genetic Code; D005821:Genetic Techniques; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics
chemical_list: D020135:Peptide Nucleic Acids