David T Hickman | PubMed Health

PubMed2006

DyNAs: constitutional dynamic nucleic acid analogues.

Dynamic cationic polymers were generated in aqueous media from functionally complementary monomers bearing nucleobase groups. (1)H NMR spectroscopy was used to follow the polycondensation reaction of the nucleobase-appended dihydrazides 1 and 2 with the dialdehydes B and C. The reversibility of these polymers was established by proton NMR spectroscopy through exchange of the dihydrazide 2 with polymer 1 B. The polymers 1 B, 2 B, 1 C, and 2 C represent dynamic biopolymers of nucleic acid type, DyNAs. Electrostatic interaction of these polymers with polyanionic entities, such as polyphosphates, polynucleotides, and polyaspartic acid, was shown to take place. It induces a change in size of the dynamic polymer, as it responds by an increase in degree of polymerization to an increase of the overall anionic charge introduced, that is, to the total electrostatic interaction.

Aldehydes↗

PubMed2004

Nucleic acid binding properties of thyminyl and adeninyl pyrrolidine-amide oligonucleotide mimics (POM).

Adeninyl POM was prepared using solid-phase peptide chemistry and shown to exhibit higher affinity for complementary DNA and RNA than the corresponding adeninyl PNA.

DNA↗

PubMed2003

Design, synthesis, conformational analysis and nucleic acid hybridisation properties of thymidyl pyrrolidine-amide oligonucleotide mimics (POM).

Pyrrolidine-amide oligonucleotide mimics (POM) 1 were designed to be stereochemically and conformationally similar to natural nucleic acids, but with an oppositely charged, cationic backbone. Molecular modelling reveals that the lowest energy conformation of a thymidyl-POM monomer is similar to the conformation adopted by ribonucleosides. An efficient solution phase synthesis of the thymidyl POM oligomers has been developed, using both N-alkylation and acylation coupling strategies. 1H NMR spectroscopy confirmed that the highly water soluble thymidyl-dimer, T2-POM, preferentially adopts both a configuration about the pyrrolidine N-atom and an overall conformation in D2O that are very similar to a typical C3'-endo nucleotide in RNA. In addition the nucleic acid hybridisation properties of a thymidyl-pentamer, T5-POM, with an N-terminal phthalimide group were evaluated using both UV spectroscopy and surface plasmon resonance (SPR). It was found that T5-POM exhibits very high affinity for complementary ssDNA and RNA, similar to that of a T5-PNA oligomer. SPR experiments also showed that T5-POM binds with high sequence fidelity to ssDNA under near physiological conditions. In addition, it was found possible to attenuate the binding affinity of T5-POM to ssDNA and RNA by varying both the ionic strength and pH. However, the most striking feature exhibited by T5-POM is an unprecedented kinetic binding selectivity for ssRNA over DNA.

Base Pairing↗