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Originally published in Science Express on 11 June 2009
Science 3 July 2009:
Vol. 325. no. 5936, pp. 73 - 77
DOI: 10.1126/science.1174577

Reports

Self-Assembling Sequence-Adaptive Peptide Nucleic Acids

Yasuyuki Ura,1 John M. Beierle,1 Luke J. Leman,1 Leslie E. Orgel,2 M. Reza Ghadiri1,*

Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.

1 Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, CA 92186, USA.

* To whom correspondence should be addressed. E-mail: ghadiri{at}scripps.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)