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.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Brudno Y,Birnbaum ME,Kleiner RE,Liu DR

doi

10.1038/nchembio.280

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

148-55

issue

2

eissn

1552-4450

issn

1552-4469

pii

nchembio.280

journal_volume

6

pub_type

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