title: Coordination-driven inversion of handedness in ligand-modified PNA.
abstract: Peptide nucleic acid (PNA) is a synthetic analogue of DNA, which has the same nucleobases as DNA but typically has a backbone based on aminoethyl glycine (Aeg). PNA forms duplexes by Watson Crick hybridization. The Aeg-based PNA duplexes adopt a chiral helical structure but do not have a preferred handedness because they do not contain a chiral center. An L-lysine situated at the C-end of one or both strands of a PNA duplex causes the duplex to preferably adopt a left-handed structure. We have introduced into the PNA duplexes both a C-terminal L-lysine and one or two PNA monomers that have a γ-(S)-methyl-aminoethyl glycine backbone, which is known to induce a preference for a right-handed structure. Indeed, we found that in these duplexes the γ-methyl monomer exerts the dominant chiral induction effect causing the duplexes to adopt a right-handed structure. The chiral PNA monomer had a 2,2':6',2''-terpyridine (Tpy) ligand instead of a nucleobase and PNA duplexes that contained one or two Tpys formed [Cu(Tpy)(2)](2+) complexes in the presence of Cu(2+). The CD spectroscopy studies showed that these metal-coordinated duplexes were right-handed due to the chiral induction effect exerted by the S-Tpy PNA monomer(s) except for the cases when the [Cu(Tpy)(2)](2+) complex was formed with Tpy ligands from two different PNA duplexes. In the latter case, the metal complex bridged the two PNA duplexes and the duplexes were left-handed. The results of this study show that the preferred handedness of a ligand-modified PNA can be switched as a consequence of metal coordination to the ligand. This finding could be used as a tool in the design of functional nucleic-acid based nanostructures.
authors: Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3890, USA.
authors: Silvia
authors: S
authors: Bezer
authors: Srinivas
authors: S
authors: Rapireddy
authors: Yury A
authors: YA
authors: Skorik
authors: Danith H
authors: DH
authors: Ly
authors: Catalina
authors: C
authors: Achim
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics; D011725:Pyridines / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013696:Temperature; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D020135:Peptide Nucleic Acids; D011725:Pyridines; D013777:Tetrazoles; C045574:1H-tetrazole; D003300:Copper; C023666:pyridine