Dr. Vagner's research expertise is in the area of design and development of compounds for in vivo pharmacologic applications and drug discovery. He has a background in organic and medicinal chemistry, with specific training in solid phase synthesis and small molecule drug discovery. This 25+ years of expertise also includes structural analysis and design of de novo ligands for various biological targets including a recent focus on multivalent ligand sand drug-ligand conjugates. Dr. Vagner's research career began in the pharmaceutical industry (Sanofi, Novo Nordisk, and SIDCCO) where he specialized in combinatorial chemistry and solid phase synthesis of small molecule libraries. During his time in the industry, he supervised teams of workers who successfully accomplished the synthesis of more than ten large libraries (with 10,000+ compounds each). During the last decade, as a director of the Ligand Discovery Laboratory at the University of Arizona BIO5 Institute, Dr. Vagner was responsible for design, synthesis, purification, characterization of compound libraries for multiple biological targets and their primary screening. Their center is based on collaboration attitude rather than as a core synthetic facility. His role in projects fluctuates from consultant to PI commitment that depends on a structure of assignment.
Currently, I am leading the Ligand Discovery Lab (LDL) at Bio5, University of Arizona. The current research projects deal with the development of ligands, inhibitors, and diagnostic probes in collaboration with the AZCC, UNMCC, TGen, Department of Radiology and Department of Biochemistry.
- Solid-phase synthesis (small organic compounds, biopolymers)
- High throughput synthesis (96-well plates)
- One-bead-one-compound (OBOC) library synthesis
- Rational design of small molecule ligands, multimeric ligands, peptidomimetics
- Lanthanide-based time-resolved fluorometry in vivo binding assay
- In vivo cell-adhesion-to-bead assay for OBOC library
- HT synthesis of labeled probes (fluorescent, DOTA-Eu)
- Logistics and QC
- Vagner, J., Barany, G., Lam, K.S., Krchnak, V., Sepetov, N.F., Ostrem, J.A., Strop, P., and Lebl, M., Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries. Proceedings of the National Acadademy of Science of the U.S.A., 93, 8194-8199 (1996).
- Cowell, S.M.; Gu, X.; Vagner, J.; Hruby, V.J. Intelligent design in combinatorial chemistry: use of designed peptide libraries to explore secondary and tertiary structures in peptides and proteins. Methods in Enzymology, 369 (Combinatorial Chemistry, Part B), 288-297 (2003).
- Handl, H.L.; Vagner, J.; Han, H.; Mash, E.; Hruby, V.J.; Gillies, R.J. Hitting multiple targets with multimeric ligands. Expert Opinion on Therapeutic Targets, 8, 565-586 (2004).
- Vagner, J., Handl, H., Gillies, R.J., Hruby, V.J. Novel strategy based on multimeric ligands for drug delivery and imaging: homooligomers of a-MSH. Bioorganic & Medicinal Chemistry Lett. ,14, 211-215 (2004).
- Handl, H.L., Vagner, J., Yamamura H.I., Hruby, V.J., Gillies, R.J. Lanthanide-based time-resolved fluorescence of in cyto ligand-receptor interactions. Analytical Biochemistry, 330, 242-250 (2004).
- Vagner, J., Handl, H.L., Monguchi, Y., Jana, U., Begay, L., Mash, E. A., Hruby, V.J., Gillies, R.J. Rigid linkers for bioactive peptides. Bioconjugate Chemistry, 17,1545-1550 (2006).
- Mayorov, A.V. Cai, M. Palmer, E.S., Dedek, M.M., Cain, J.P., Van Scoy, A.P., Tan, B. Vagner, J., Trivedi, D., Hruby, V.J., Structure-Activity Relationships of Cyclic Lactam Analogues of a-MSH. Targeting the Human Melanocortin-3 Receptor.Journal of Medicinal Chemistry 51, 187-195 (2008).
- Vagner J., Xu L., Handl H.L., Josan J.S., Morse D.L., Mash E.A., Gillies R.J., and Hruby V.J., Heterobivalent Ligands Crosslink Multiple Cell-Surface Receptors: The Human Melanocortin-4 and d-Opioid Receptors. Angewandte Chemie Intl. Ed. 47, 1685-1688 (2008).
- Black, K.C., Kirkpatrick, N.D., Troutman, T.S., Xu, L., Vagner, J., Gillies, R.J., Barton, J.K., Utzinger, U., Romanowski, M. Gold nanorods targeted to delta opioid receptor: plasmon-resonant contrast and photothermal agents. Molecular Imaging 7, 50-57 (2008).
- Vagner, J., Qu, H., Hruby, V.J. Peptidomimetics, a synthetic tool of drug discovery. Current Opinion in Chemical Biology 12(3), 292-296 (2008).
The LDL proram relies on an existing information flow from TGen, and collaborations with other groups:
July 2005 – present
University of Arizona, Bio5, Tucson, AZ, Associate Research Professor, Director of Ligand Discovery Lab; Advanced Research Institute for Biomedical Imaging (member)
High throughput synthesis and screening of diverse chemical libraries.
Design of ligands for disease diagnosis and therapy.
Design and synthesis of labeled biomarkers and pharmaceuticals.
May 2002 – June 2005
University of Arizona, Bio5, Tucson, AZ, Assistant Research Professor (Organic Chemist)
Scientific advisers: Prof. Robert J. Gillies and Prof. Victor J. Hruby
The design and solid-phase synthesis of multimeric ligands for binding to the combination of epitopes specific to human cancer cells.
December 1998 – September 2001
SIDDCO, Tucson, AZ, Scientific Fellow 5 (Synthetic Organic Chemist/Principal Scientist)
The design and synthesis of combinatorial libraries in a format suitable for high throughput screening as potential drugs. The development and optimization of reactions and scaffolds on solid-phase supports (the protocols to be used in the production of combinatorial libraries).
November 1995 – September 1998
Novo Nordisk A/S, Copengagen, Denmark, Research Chemist
The design and synthesis small combinatorial libraries – arrays of organic compounds, and multiple synthesis in automatic devices. The development of reactions on solid-phase support, multi-step organic syntheses, purifications and analyses of products.
October 1992 - October 1995
University of Minnesota, Department of Chemistry, Minneapolis, USA; Postdoctoral Fellow
Scientific adviser: Prof. George Barany
The solid-phase peptide synthesis involving the synthesis of defensins, orthogonal protection schemes, acid-labile handles and protecting groups. The combinatorial chemistry for synthesis of non-peptide libraries.