- Research Professor
- Director, Ligand Discovery Laboratory
- Research Associate Professor, Pharmacology
No activities entered.
No activities entered.
Directed ResearchBIOC 492 (Spring 2018)
Honors Independent StudyBIOC 299H (Spring 2018)
Honors Independent StudyBIOC 399H (Spring 2018)
Senior CapstoneBIOC 498 (Spring 2018)
Directed ResearchBIOC 492 (Fall 2017)
Senior CapstoneBIOC 498 (Fall 2017)
- Vagner, J., Boitano, S., Flynn, A. N., Schulz, S. M., Hoffman, J., Price, T. J., & Vagner, J. -. (2011). Potent agonists of the protease activated receptor 2 (PAR2). Journal of medicinal chemistry, 54(5).More infoNovel peptidomimetic pharmacophores to PAR(2) were designed based on the known activating peptide SLIGRL-NH(2). A set of 15 analogues was evaluated with a model cell line (16HBE14o-) that highly expresses PAR(2). Cells exposed to the PAR(2) activating peptide with N-terminal 2-furoyl modification (2-furoyl-LIGRLO-NH(2)) initiated increases in intracellular calcium concentration ([Ca(2+)](i) EC(50) = 0.84 μM) and in vitro physiological responses as measured by the xCELLigence real time cell analyzer (RTCA EC(50) = 138 nM). We discovered two selective PAR(2) agonists with comparable potency: compound 1 (2-aminothiazol-4-yl; Ca(2+) EC(50) = 1.77 μM, RTCA EC(50) = 142 nM) and compound 2 (6-aminonicotinyl; Ca(2+) EC(50) = 2.60 μM, RTCA EC(50) = 311 nM). Unlike the previously described agonist, these novel agonists are devoid of the metabolically unstable 2-furoyl modification and thus provide potential advantages for PAR(2) peptide design for in vitro and in vivo studies. The novel compounds described herein also serve as a starting point for structure-activity relationship (SAR) design and are, for the first time, evaluated via a unique high throughput in vitro physiological assay. Together these will lead to discovery of more potent agonists and antagonists of PAR(2).
- Vagner, J., Hruby, V. J., & Vagner, J. -. (2006). High throughput synthesis of peptides and peptidomimetics. Chimica oggi, 24(4).More infoPeptide synthesis has been developed into one of the most efficient synthetic procedures in organic chemistry. The problems of orthogonal functional group protection and amide bond formation without racemization have been developed in a number of ingenious strategies. Optimization, in particular, has been achieved in stepwise solid phase synthesis. This in turn made possible the development of combinatorial synthesis allowing the synthesis of millions of peptide compounds of high purity in a few days. A variety of methodologies and strategies have been developed and continue to be developed to determine structures and to evaluate peptides and peptidomimetics. The development of methods for solid phase synthesis of a variety of organic and inorganic structures using similar strategies as in peptide synthesis are being vigorously pursued. However, existing instrumentation and technology is not sufficient to cover current demands for peptides, and thus new approaches and technologies for cost-effective synthesis of peptide arrays are needed.