Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency: a study on alpha4beta2 nicotinic ligands

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

doi:10.1021/jm801060h

Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency: a study on alpha4beta2 nicotinic ligands

J Med Chem. 2009 Apr 23;52(8):2311-6. doi: 10.1021/jm801060h.

Authors

Paolo Tosco¹, Philip K Ahring, Tino Dyhring, Dan Peters, Kasper Harpsøe, Tommy Liljefors, Thomas Balle

Affiliation

¹ Department of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Torino, Italy.

PMID: 19301898
DOI: 10.1021/jm801060h

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Calcium / metabolism
Cell Line
Drug Partial Agonism
Humans
Ligands
Models, Molecular*
Molecular Conformation
Nicotine / metabolism
Nicotinic Agonists / chemistry
Nicotinic Agonists / metabolism
Nicotinic Agonists / pharmacology*
Pyridines / chemistry
Pyridines / metabolism
Pyridines / pharmacology
Quantitative Structure-Activity Relationship*
Receptors, Nicotinic / metabolism*

Substances

Ligands
Nicotinic Agonists
Pyridines
Receptors, Nicotinic
nicotinic receptor alpha4beta2
Nicotine
Calcium