Special Issue "Nucleoside Analogues"
A special issue of Molecules (ISSN 1420-3049).
Deadline for manuscript submissions: closed (30 April 2011)
Prof. Dr. Ramachandra S. Hosmane (Website)
Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA
Interests: heterocycles; nucleosides; nucleotides; medicinal chemistry; organic synthesis; purines; pyrimidines; enzymes of purine and pyrimidine metabolism; bioorganic synthesis
Analogues of natural nucleosides have long played pivotal roles in the treatment of viral infections and cancer. A vast majority of FDA approved drugs to treat viral infections are nucleoside analogues, including but not limited to AZT, ddI, ddC, FTC, 3TC (HIV), entecavir, lamivudine, telbuvidine (HBV), and acyclovir (HSV). In addition, a number of drugs currently under clinical development for treating HCV infection, which fall under the category of polymerase inhibitors, are nucleoside analogues. With regard to chemotherapy, nucleoside or nucleobase analogues were among the first to be introduced for the treatment of cancer. Some examples of FDA-approved anticancer nucleosides/nucleobases include Ara-C (AML/leukemia), 5-FU (skin cancer), and gemcitabine (breast, pancreatic, lung, and ovarian cancers). A number of these nucleoside analogues act as antimetabolites, compete with natural nucleosides, and interact with a large number of intracellular targets to induce cytotoxicity. A lot of work is currently underway in identification and characterization of nucleoside transporters and the enzymes of nucleoside metabolism. Many of these enzyme inhibitors are derived from nucleoside framework, and are targeted to reverse transcriptases and other polymerases, deaminases, kinases, and hydrolases, and have found additional uses in a wide variety of bacterial infections such as malaria and tuberculosis. A number of nucleoside analogues get incorporated during replication or DNA excision repair synthesis, leading to chain termination. Recent research on DNAzymes, which cleave at predetermined sequences within RNA, suggests that incorporation of locked nucleoside analogues into DNAzymes improves their ability to gain access and cleave at highly-structured RNA targets. Furthermore, biophysical investigations of certain locked nucleoside analogues have revealed that they possess hybridization and mismatch discrimination attributes similar to those of locked nucleic acid (LNA) but with greatly improved resistance to exonuclease digestion. Considerable advances have also been made in the area of adenosine receptor agonists/antagonists, which play significant roles in regulation of myocardial oxygen consumption, coronary blood flow, antiinflammatory effects, release of neurotransmitters, and control of immune responses. A vast majority of these agonists/antagonists are derived from adenosine or xanthine family. Finally, a lot of research of mainly academic interest is being carried out on nucleoside analogues as potentially new genetic alphabets. With non-standard hydrogen-bonding topologies, shape complementarity, and/or hydrophobic interfaces, these unnatural bases could pair with complementary natural or unnatural bases to confer enough selectivity and efficiency during transcription, translation, and replication, thus expanding the genetic information. Articles falling in any of these described or related areas are welcome for inclusion of this special issue of Molecules on Nucleoside Analogues, to be published by MDPI, Switzerland.
Prof. Dr. Ramachandra S. Hosmane
- antiviral compounds
- anticancer compounds
- enzyme inhibitors
- receptor agonists/antagonists
- DNA/RNA building blocks
- biophysical applications