Stewart W. Schneller
Professor and Dean
Indiana University, Ph.D., 1968
Stanford University, NIH Postdoctoral Fellow, 1968-1970
University of Massachusetts, Postdoctoral Associate, 1970-1971
schnest@auburn.edu
(334) 844-6963
Organic Chemistry: synthesis of nucleosides and nucleotides
S-Adenosyl-L-methionine (AdoMet, Fig. 1) -dependent transmethylations play an important role in regulating various biochemical and physiological processes. One such process that is the focus of the Schneller laboratory is the formation of the methylated capped 5'-terminus of eukaryotic and viral mRNA. These unique structures consist of (i) an N-7 methylguanosine residue linked at the 5'-hydroxyl group by a triphosphate to the 5'-end of the mRNA strand and (ii) a methyl substituent on the 2'-hyroxyl of the penultimate nucleotide (Fig. 2). Such methylations, which are catalyzed by N-7 methyltransferases and nucleoside 2'-methyltransferases that use AdoMet as the co-factor, are necessary for a fully functional mRNA.
As part of a program designed to study the mechanism of the mRNA methyltransferases to develop methylation inhibitors, we are investigating transition state analogs of the methyl transfer (Fig. 3) and analogs of the AdoMet co-factor (Fig. 4).
The research is funded by the National Institutes of Health for the development of new antiviral agents that will act by inhibiting viral mRNA methylation.
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Current research on Antiviral drug development
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Selected Publications:
Yin, X.Q.; Rajappan, V.P.; Roy A; Schneller, S.W. A facile synthesis of (-)-(4R,5R)-4,5-(isopropylidenedioxy)-2-cyclopentenone, a useful precursor to D-like carbanucleosides. Synth. Commun. 2003, 33, 1477-1481. [PDF]
Tuncbilek, M.; Schneller, S.W. 9-Deaza-5 '-noraristeromycin. Bioorg. Med. Chem. 2003, 11, 3331-3334. [PDF]
Rajappan, V.P.; Schneller, S.W. 5 '-amino-5 '-deoxyaristeromycin and its antiviral properties. Bioorg. Med Chem. 2003, 11, 5199-5201. [PDF]
Roy, A.; Schneller, S.W. 4 '- and 1 '-methyl-substituted 5'-norcarbanucleosides. J. Org. Chem. 2003, 68, 9269-9273. [PDF]
Tuncbilek, M.; Schneller, S.W. 5 '-nor carbocyclic ribavirin. Nucleosides, Nucleotides Nucleic Acids 2003, 22, 1995-2001. [PDF]
Yin, X.Q.; Schneller, S.W. 1-deaza-5'-noraristeromycin. Nucleosides, Nucleotides Nucleic Acids 2004, 23, 67-76. [PDF]
Yin, X.Q.; Schneller, S.W. 5'-noraristeromycin possessing a C-1' cyclopentyl double bond: a new carbanucleoside structural prototype. Tetrahedron 2004, 60, 3451-3455. [PDF]
Yang, M.; Ye, W.; Schneller, S.W. Preparation of carbocyclic S-adenosylazamethionine accompanied by a practical synthesis of (-)-aristeromycin. J. Org. Chem. 2004, 69, 3993-3996. [PDF]
Zhou, J.; Yang, M.;Schneller, S.W. A model study to carbocyclic formycin A and B analogues. Tetrahedron Lett. 2004, 45, 8233-8234. [PDF]
Yang, M.; Zhou, J.; Schneller S.W. An efficient synthesis of (-)-3-deazaaristeromycin. Tetrahedron Lett. 2004, 45, 8981-8982. [PDF]
Yang, M.; Schneller, S.W. 5'-Homoaristeromycin. Synthesis and antiviral activity against orthopox viruses. Bioorg. Med. Chem. Lett. 2005, 15, 149-151. [PDF]
Yang, M.; Schneller, S.W. Amino substituted derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin. Bioorg. Med. Chem., 2005, 13, 877-882. [PDF]
Yin, X.-q.; Schneller, S. W. 5'-Noraristeromycin derivatives isomeric to aristeromycin and 2'-deoxyristeromycin. Tetrahedron 2005, 61, 1839-1843. [PDF]
Roy, A.; Schneller, S. W.; Keith, K. A.; Hartline, C. B.; Kern, E. R. The 4',4'- Difluoro analog of 5'-noraristeromycin: a new structural prototype for possible antiviral drug development toward orthopoxvirus and cytomegalovirus. Bioorg. Med. Chem. 2005, 13, 4443-4449. [PDF]
Yang, M.; Schneller, S. W.; Korba, B. 5' Homoneplanocin A inhibits hepatitis B and hepatitis C. J. Med. Chem. 2005, 48, 5043-5046. [PDF]
Yin, X.-q.; Schneller, S. W. Isomers of neplanocin A and 2'- deoxyneplanocin A possessing a C-1'/C-6' double bond. Tetrahedrom Lett. 2005, 46, 1927-1929. [PDF]
Hausmann, S.; Zheng, S.; Fabrega, C.; Schneller, S. W.; Lima, C. D.; Shuman, S. Encephalitozoon cuniculi mRNA (guanine N-7) methyltransferase. J. Biol. Chem. 2005, 280, 20404-20412. [PDF]
Roy, A,; Schneller, S. W. An unusual occurrence on attempted purine C-8 electrophilic flourination of 5'-noraristeromycin. Organic Lett. 2005, in press.