Adaptive Synthetic Peptides

Newly reported self-assembling oligomers can store instructions for biological life by using nucleobases in the same way as DNA or RNA. These synthetic peptides also have the unusual ability to dynamically swap the nucleobases to meet their needs, without modifying the oligomeric backbone (Science, DOI: 10.1126/science.1174577). M. Reza Ghadiri of Scripps Research Institute and colleagues built the dipeptide backbone of the oligomers with alternating cysteine moieties. Each cysteine's sulfhydryl group can reversibly anchor a variety of nucleic acid bases that have been modified to undergo transthioesterification reactions. The resulting thioester peptide-nucleic acid hybrids, called tPNAs, can pair with nucleic acid bases from similar synthetic oligomers and with RNA and DNA. But what makes the work "truly outstanding," comments John D. Sutherland, a chemist at the University of Manchester, in England, is that when the tPNAs are mixed in a beaker containing a pool of nucleobases and DNA that does not possess complementary bases, the tPNA oligomer will substitute bases so that it can optimally form base pairs with the DNA. These adaptive oligomers provide food for thought for researchers studying origin-of-life chemistry or developing "biomaterials capable of dynamic sequence repair and adaptation," the Scripps researchers note.