Associate Professor of Pharmaceutical Sciences
B.S., Pharmacy, University of Athens, Greece
Ph.D., Medicinal Chemistry/Computational Chemistry, University of North Carolina, Chapel Hill
Post-doctoral, Biomedical Engineering, University of Washington, Seattle
Dr. Kontoyianni’s laboratory focuses on the classification of structural data pertaining to drug-protein complexes, development of computational tools to better understand ligand recognition by macromolecular targets, and drug discovery approaches to specific disease areas. Specifically, one major area in the laboratory involves the investigation of protein binding sites and requirements for binding. We correlate the nature of binding pockets with small molecule variables to predict potential for drug-protein associations, and also navigate through protein families to predict putative protein function. This project enables us to link protein targets with unannotated small molecules or assign chemical compounds to unliganded macromolecular targets. Another thrust in the laboratory involves ligands and their involvement in modulating protein properties for disease-related targets, such as somatostatin, chemokines, and cytochrome P450s. Integrative approaches such as model-building, ensemble docking and molecular dynamics are being employed. Finally, we are interested in examining and systematizing sets of known drugs against respective homologous protein families in order to extrapolate common scaffolds that can then be used as starting points toward building drugs piece-by-piece. The advantage of starting with smaller molecules is that it enables us to identify structures with more ideal pharmacokinetic properties, and a higher chance of optimal binding to the protein. This approach derives its knowledge base from a combination of compound and protein space, rather than a generalized chemical selection.
1. Kontoyianni, M. G Protein Coupled Receptors and Structure-Based Advances, 2016, Curr. Topics Med. Chem. 16, 1-16.
2. Masini, T.; Lacy, B.; Monjas, L.; Hawksley, D.; de Voogd, A. R.; Illarionov, B.; Iqbal, A.; Leeper, F. J.; Fischer, M.; Kontoyianni, M.; Hirsch, A. K. H. Structural rationalization of the activity differences of thiamine derivatives as potent inhibitors of two orthologues of DXS, Org. Biomol. Chem. 2015, 13, 11263.
3. Kota, K.; Afrasiabi, M.; Lacy, M.; Kontoyianni, M.; Crider, M.; Song, D.; Kuzhikandathil, E.V. “cis and trans Isomers of 8-hydroxy-3-(n-propyl)-1,2,3a,4,5,9b-hexahydro-1 H-benz[e]indole Differentially Affect the Activation and Signaling Properties of Dopamine D2 and D3 Receptors”, Pharmacol. Res. 2015, 99, 174-184.
4. Hayes, C., Ansbro, D., and Kontoyianni, M. Elucidating Substrate Promiscuity in the Human Cytochrome 3A4, J. Chem. Inf. Model. 2014, 54, 857-869.
5. Sandoval K.E., Witt K.A., Crider A.M., Kontoyianni M. Somatostatin Receptor-4 Agonists as Candidates for Treatment of Alzheimer’s Disease. Frontiers in Drug Design and Discovery, 2014, 6, 566-597.