New tools for G-protein coupled receptor (GPCR) drug discovery: combination of baculoviral expression system and solid state NMR.
Biotechnology using molecular biology, biochemistry, biophysics, and computational approaches provides an alternative approach for classical pharmacological screening to look at ligand-receptor interactions and receptor specificity, which should support the design of selective drugs based on detailed structural principles. This review addresses specific approaches to study function, structure and relevance of a major pharmaceutical target, namely the G-Protein Coupled Receptors (GPCRs). The main aim of this review has been to exploit and combine GPCR over-expression in a baculoviral expression system with solid-state MAS NMR (ssNMR) approaches for the elucidation of electronic structures of the coordinating ligands/drugs and their modes of interactions with the GPCRs. This review summarizes the approaches, possible future experiments and developments using the above combination of tools for GPCR drug discovery.
Ratnala
Venkata R P
VR
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RALeiden, The Netherlands. ratnala@stanford.edu
D016367:Baculoviridae / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled