Design, synthesis, conformational analysis and nucleic acid hybridisation properties of thymidyl pyrrolidine-amide oligonucleotide mimics (POM).
Org Biomol Chem
; 1(19): 3277-92, 2003 Oct 07.
Article
em En
| MEDLINE
| ID: mdl-14584791
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Pirrolidinas
/
Timidina
/
Desenho de Fármacos
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Pareamento de Bases
/
Materiais Biomiméticos
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2003
Tipo de documento:
Article