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