Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes.

ABSTRACT: Neuronal nicotinic receptors, encoded by nine genes of the alpha and three of the beta type of subunits, and whose gene products assemble in distinct permutations as pentameric molecules, constitute a fertile area for structure-guided drug design. Design strategies are augmented by a wide variety of peptide, alkaloid and terpenoid toxins from various marine and terrestrial species that interact with nicotinic receptors. Also, acetylcholine-binding proteins from mollusks, as structural surrogates of the receptor that mimic its extracellular domain, provide atomic resolution templates for analysis of structure and response. Herein, we describe a structure-guided approach to nicotinic ligand design that employs crystallography of this protein as the basic template, but also takes into conside

SUBMITTER: Taylor P 

PROVIDER: S-EPMC3341175 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature