Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency: a study on alpha4ß2 nicotinic ligands

Research output: Contribution to journalJournal articleResearchpeer-review

Paolo Tosco, Philip K Ahring, Tino Dyhring, Dan Peters, Kasper Harpsøe, Tommy Liljefors, Thomas Balle

Complementary 3D-QSAR modeling of binding affinity and functional potency is proposed as a tool to pinpoint the molecular features of the ligands, and the corresponding amino acids in the receptor, responsible for high affinity binding vs those driving agonist behavior and receptor activation. This approach proved successful on a series of nicotinic alpha(4)beta(2) ligands, whose partial/full agonist profile could be linked to the size of the scaffold as well as to the nature of the substituents.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume52
Issue number8
Pages (from-to)2311-2316
ISSN0022-2623
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Binding Sites; Calcium; Cell Line; Drug Partial Agonism; Humans; Ligands; Models, Molecular; Molecular Conformation; Nicotine; Nicotinic Agonists; Pyridines; Quantitative Structure-Activity Relationship; Receptors, Nicotinic

ID: 13086822