title: Searching for allosteric effects via QSAR. Part II.
abstract: Allosteric interactions have in the past been established by means of X-ray crystallography or careful study of a single molecule at a variety of concentrations. Here we report a method for using QSAR to establish a change in reaction mechanism by establishing an inversion point. That is, as polarizability of a member of a congeneric set of compounds is increased (as measured by CMR), activity at first decreases until, at the inversion, activity turns around and increases. Out of 23 examples, 14 have inversion points of 10+/-1. This includes a wide variety of receptors such as thrombin, 5-HT, dopamine, and tyrosine kinase acting with a variety of ligands.
authors.affiliation: Department of Chemistry, Pomona College, CA 91711, Claremont, USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Garg
authors.forename: Alka
authors.initials: A
authors.lastname: Kurup
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Mekapati
authors.forename: Corwin
authors.initials: C
authors.lastname: Hansch
mesh_terms: D000465:Algorithms; D000818:Animals; D016466:CHO Cells; D002268:Carboxypeptidases / Q000737:chemistry; D043422:Carboxypeptidases A; D006224:Cricetinae; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D066246:ErbB Receptors / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D008024:Ligands; D051379:Mice; D008826:Microbial Sensitivity Tests; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D043587:Receptor, Muscarinic M3; D011955:Receptors, Drug / Q000737:chemistry / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D043587:Receptor, Muscarinic M3; D011955:Receptors, Drug; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D015842:Serine Proteinase Inhibitors; D059005:Topoisomerase II Inhibitors; C102718:metabotropic glutamate receptor 3; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D066246:ErbB Receptors; D004851:Epoxide Hydrolases; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D019272:Leukocyte Elastase; D013917:Thrombin