Searching for allosteric effects via QSARs.
A study of our database of 7,000 QSARs involving chemical-biological interaction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreases with increase in MR and then increases. Two of the examples are for enzymes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a change in a receptor unit that allows for a new mode of interaction.
Hansch
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Department of Chemistry, Pomona College, Claremont, CA 91711, USA.
Garg
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Kurup
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D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry; D019992:Databases as Topic; D006801:Humans; D020128:Inhibitory Concentration 50; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry; D012031:Refractometry; D014357:Trypsin / Q000737:chemistry; D014361:Trypsin Inhibitors / Q000737:chemistry
D016861:Cyclooxygenase Inhibitors; D011956:Receptors, Cell Surface; D014361:Trypsin Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D014357:Trypsin