Determination of a Sequencing Methodology for Sequence-Defined Oligourethanes

Sequence-defined polymers, such as DNA and proteins, are macromolecules in which the order of monomers is specified; this ordering gives them a distinct structure and thus a distinct function. Foldamers are synthetic molecules that are of interest due to their similarities to proteins, as they are able to adopt defined secondary structures in solution based on their primary sequences. This dependence on primary sequence means that the structures and therefore the functions of foldamers have the potential to be tuned. Unlike DNA and proteins, though, foldamers are currently incapable of being sequenced and are difficult to characterize. This work, therefore, is focused on the solid-phase synthesis of novel oligourethanes for their use as foldamers and the optimization of their sequencing as a facile characterization method. Previously our group has shown that oligourethanes composed of reduced β-amino acid monomers can be “unzipped.” Their sequences can be retroactively deduced via the monitoring and characterization of the parent chain as each cyclic product is clipped off the terminus of the chain, similar to Edman degradation of peptides. Currently we are exploring this chemistry with “peptoid” monomers in order to determine the scope of the sequencing method and to expand the secondary structures that can be achieved. These sequence-defined oligourethanes have the potential to be used in therapeutics, materials, and catalysis.