FWP Institutskolloquium: "Current studies of neuronal nicotinic acetylcholine receptor allosteric modulator sites: Toward subtype-specific probes"

Date

May 9, 2014

Time

2:00 PM - 3:30 PM

Speaker

Mark Levandoski

Affiliation

Associate Professor of Chemistry,Grinnell College, Grinnell, Iowa, USA

Language

en

Main Topic

Physik

Other Topics

Physik

Host

Prof. Dr. Peter BrustAbteilungsleiter NeuroradiopharmakaInstitut für Radiopharmazeutische KrebsforschungForschungsstelle LeipzigTel. 0341-234 179 4610

Description

We study allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs), an important family of ligand-gated ion channels that mediate the effects of nicotine. We have demonstrated that a site homologous to the canonical agonist site, but occurring in the non-canonical beta(+)/alpha(-) subunit interface, harbors modulatory activity for certain alkaloid-containing compounds. Our work and other recent reports in the literature are establishing the generality of the idea that all nAChR subunit interfaces are potential ligand binding sites. In on-going work, we are 1) further defining the specificity of the sites we have studied most, both in terms of protein molecular determinants and small molecule pharmacophores; and 2) addressing, from a mechanistic perspective, the number and relative arrangement of agonist and modulator sites required for optimal channel activation. Our results, as well as the theoretical framework in which we interpret them, will have impacts on our understanding of nAChR subtypes specificity and rational drug design.

Last modified: May 9, 2014, 9:40:05 AM