Centers - Nano-medicine - Dr. Stanislav Engel



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Macromolecular Crystallography Research Center (MCRC)

Dr. Stanislav Engel

Nano-medicine

Scientific Research

nibn

Dr. Stas Engel

Ph.D.: Ben-Gurion University, Israel
Post-doctorate: The National Institutes of Health, USA
Position: Lecturer

Department of Clinical Biochemistry

Faculty of Health Sciences

E-mail: engels@bgu.ac.il

Interaction between bio-molecules as target for pharmacological intervention

Background

Protein-protein interactions (PPI) play an essential role in virtually all cellular processes. In biological systems, information is conveyed by the action of small-molecule messengers (Ca²⁺, cAMP, neurotransmitters, etc.) and via PPI. While mimetics of the former are widely used to intervene in the functions of biological systems, we have only a rudimentary capacity to manipulate PPI. Increasingly, PPI are appreciated as potential targets for the development of selective tools to modulate the functions of biological systems. PPI targeting using drugs may represent a new strategy to combat diseases that have remained intractable through conventional therapies.

Current research

1. Functional mimetics of the extra- and intracellular domains of G protein coupled receptors (GPCR) as a tool for studying the structural basis of GPCR interaction with molecular targets and drug discovery.

2. Combinatorial in vitro selection methods to identifying active compounds targeting protein-protein interactions, in particular formation of GPCR/G protein complexes.

3. Molecular modeling in structure-based drug discovery.

Selected publications

I.G. Tikhonova, R.B. Best, S. Engel, G. Hummer, M.C. Gershengorn and S. Costanzi, Atomistic insights into rhodopsin activation from a dynamic model, Journal of the American Chemical Society, 130(31):10141-10149 (2008)

S. Engel, A. Skoumbourdis, J. Childress, S. Neumann, J.R. Deschamps, C.J. Thomas, A.O. Colson, C. Stefano and M.C. Gershengorn, A Virtual Screen for Diverse Ligands: Discovery of Selective G Protein-Coupled Receptor Antagonists, Journal of the American Chemical Society, 130(15), 5115–5123 (2008)

I.G. Tikhonova, C.S. Sum, S. Neumann, S. Engel, B.M. Raaka, S. Costanzi and M.C. Gershengorn, Discovery of novel agonists and antagonists of the free fatty acid receptor (FFAR1) using virtual screening, Journal of Medicinal Chemistry, 51(3), 625–633 (2008)

C.S. Sum, I.G. Tikhonova, S. Neumann, S. Engel, B.M. Raaka, S. Costanzi and M.C. Gershengorn, Identification of Residues Important for Agonist Recognition and Activation in GPR40, Journal of Biological Chemistry, 282(40): 29248-29255 (2007)

S. Engel, S. Neumann, N. Kaur, V. Monga, R. Jain, J. Northup and M.C. Gershengorn, Low Affinity Analogs of Thyrotropin-Releasing Hormone are Super-Agonists, Journal of Biological Chemistry, 281(19):13103-13109 (2006)

Update Date: 02/05/2012