title: Duplex oligomers defined via covalent casting of a one-dimensional hydrogen-bonding motif.
abstract: Hydrogen-bonded tapes comprised of monomeric molecular precursors are used to define structural parameters for the design of related oligomers encoded with predetermined modes of assembly. Application of this "covalent casting" strategy vis-à-vis the one-dimensional H-bonding motif expressed by 2-amino-4,6-dichlorotriazine has enabled the design of high-affinity duplex molecular strands. Dimeric, trimeric, and tetrameric duplex oligomers are prepared through an iterative synthetic protocol involving sequential homologation of the oligo(aminotriazine). The mode of assembly and interstrand affinity of homologous oligomers are established in solution by (1)H NMR dilution experiments, isothermal titration calorimetry (ITC), vapor pressure osmometry (VPO), cross-hybridization experiments involving the analysis of dye-labeled strands via thin-layer chromatography (TLC), and in the solid state by X-ray crystallographic analysis. Binding free energy per unimer (-Delta G degrees/n) increases significantly upon extension from monomer to dimer to trimer, signifying a strong positive cooperative effect. Nanomolar binding affinity (K(d) = 1.44 +/- 0.50 nM) was determined for the duplex trimer by ITC in 1,2-dichloroethane at 20 degrees C. In-register duplex formation is not observed for the tetramer, which appears to adopt an alternative binding mode. These data give insight into the structural and interactional features of the oligomers required for high-affinity, high-specificity binding and define a platform for the design of second-generation systems and related duplex strands for use in nanoscale assembly.
authors: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
authors: Eric A
authors: EA
authors: Archer
authors: Michael J
authors: MJ
authors: Krische
mesh_terms: D002151:Calorimetry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry*; D013698:Templates, Genetic; D014227:Triazines / Q000737:chemistry*
chemical_list: D011108:Polymers; D014227:Triazines; D004247:DNA