title: DNA-templated polymerization of side-chain-functionalized peptide nucleic acid aldehydes.
abstract: The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step toward the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities.
authors.affiliation: Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Kleiner
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Brudno
authors.forename: Michael E
authors.initials: ME
authors.lastname: Birnbaum
authors.forename: David R
authors.initials: DR
authors.lastname: Liu
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000447:Aldehydes; D020135:Peptide Nucleic Acids; D011108:Polymers; D004247:DNA