Conformational properties of shape modified nucleosides--fleximers

Journal of the American Chemical Society
Matjaz PolakJanez Plavec

Abstract

A detailed (1)H NMR conformational study complemented with ab initio computations was performed in solution on fleximer nucleosides 1, 3, and 5 in relation to their natural counterparts. The substitution of the purine nucleobase found in the natural nucleosides with a more flexible two-ring heterocyclic system strongly increased the population of anti conformation around the glycosidic bond. This was accompanied by a large shift toward a north-type sugar conformation, which was explained by the interplay of anomeric, gauche, and steric effects. The formal separation of the bicyclic purine base into its imidazole and pyrimidine moieties allows for formation of a hydrogen bond between the NH(2) and 2'-OH groups and facilitates favorable conjugation between the two heterocyclic rings. Our results show that the interplay of stereoelectronic effects, combined with the flexibility of the nucleobase and possible conjugation effects within the nucleobase, plays a crucial role in the search for shape-mimic nucleosides that will interact with flexible binding sites.

References

Sep 16, 1998·Current Opinion in Chemical Biology·S Agrawal, Q Zhao
May 11, 2002·The Journal of Organic Chemistry·Katherine L SeleyStephen Quirk
Oct 10, 2002·Bioorganic & Medicinal Chemistry Letters·Scott M UlrichKevan M Shokat
Jun 5, 2003·Bioorganic & Medicinal Chemistry Letters·Katherine L SeleyAsmerom Hagos

❮ Previous
Next ❯

Citations

Jan 27, 2011·Physical Chemistry Chemical Physics : PCCP·Ali EbrahimiSophia Bazzi
Dec 19, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sarah C ZimmermannKatherine L Seley-Radtke
Dec 22, 2009·Organic & Biomolecular Chemistry·Feng ZhengFeng-Ling Qing
Feb 23, 2018·Antiviral Chemistry & Chemotherapy·Katherine Seley-Radtke
Jan 4, 2020·Chembiochem : a European Journal of Chemical Biology·Sophie Vichier-GuerreKatherine L Seley-Radtke
Aug 25, 2020·Chemistry of Heterocyclic Compounds·Mikhail V Chudinov
Jul 4, 2012·Organic & Biomolecular Chemistry·André H St AmantRobert H E Hudson
Sep 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mary K YatesKatherine L Seley-Radtke
Apr 15, 2008·Soft Matter·Francesca Baldelli BombelliPiero Baglioni
Jun 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Laura AlbrechtStacey D Wetmore
Nov 1, 2020·Bioorganic & Medicinal Chemistry·Joy E ThamesKatherine L Seley-Radtke
May 4, 2017·Bioorganic & Medicinal Chemistry Letters·Mary K YatesKatherine L Seley-Radtke
Mar 6, 2010·The Journal of Physical Chemistry. B·Andrea L MillenStacey D Wetmore
Apr 2, 2008·The Journal of Physical Chemistry. a·Andrea L MillenStacey D Wetmore
Jul 15, 2006·The Journal of Physical Chemistry. a·Alma B Bardon, Stacey D Wetmore
Sep 6, 2008·The Journal of Physical Chemistry. B·Linda A LaitStacey D Wetmore
Feb 26, 2005·The Journal of Organic Chemistry·Katherine L SeleyPeter I O'Daniel
Aug 30, 2005·Bioorganic & Medicinal Chemistry·Jean-Paul DesaulniersChristine S Chow
Jul 2, 2021·Organic & Biomolecular Chemistry·Anastasia KhandazhinskayaElena Matyugina
Jan 30, 2007·Journal of the American Chemical Society·Kewen M SunRichard A Manderville
May 12, 2006·The Journal of Physical Chemistry. a·Christopher K McLaughlinRichard A Manderville

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.