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Conformational properties of shape modified nucleosides--fleximers
Matjaz Polak1, Katherine L Seley, Janez Plavec
1Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, POB 660, SI-1001 Ljubljana, Slovenia.
Journal of the American Chemical Society
|July 1, 2004
Summary
Fleximer nucleosides exhibit increased anti conformation and north-type sugar conformation due to a flexible nucleobase. These findings are crucial for designing shape-mimic nucleosides targeting flexible binding sites.
Area of Science:
- Medicinal Chemistry
- Organic Chemistry
- Computational Chemistry
Background:
- Natural nucleosides are vital components of DNA and RNA.
- Understanding nucleoside conformation is key to drug design.
- Fleximer nucleosides offer modified structures for potential therapeutic applications.
Purpose of the Study:
- To investigate the solution-state conformation of fleximer nucleosides.
- To compare the conformational properties of fleximer nucleosides with natural counterparts.
- To elucidate the stereoelectronic factors governing nucleoside conformation.
Main Methods:
- Solution-state (1)H Nuclear Magnetic Resonance ((1)H NMR) spectroscopy.
- Ab initio computational chemistry.
- Conformational analysis of nucleoside analogues.
Main Results:
- Fleximer nucleosides show a significantly higher population of the anti conformation around the glycosidic bond compared to natural nucleosides.
- A pronounced shift towards a north-type sugar pucker was observed in fleximer nucleosides.
- Hydrogen bonding between nucleobase moieties and favorable conjugation were identified as key factors influencing conformation.
Conclusions:
- The flexibility of the nucleobase and stereoelectronic effects critically influence nucleoside conformation.
- Fleximer nucleosides exhibit distinct conformational preferences that can be exploited in drug discovery.
- These findings guide the rational design of novel nucleoside analogues for interacting with flexible biological targets.
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