Multiple drug binding sites

C. F., Mistry, P., Charlton, P., Caliaghan, R., Communication between multiple drug binding sites on P-glycoprotein, Mol. Pharmacol. 2000, 58, 624-632. 

Communication between multiple drug binding sites on P-glycoprotein. Molecular Pharmacology, 58, 624—632. 

The involvement of P-gp in the multidrug resistance phenotype has prompted extensive study to uncover the mechanism of this polyspccificity. Two possibilities are most likely (i) the presence of a single domain to which drugs display a loose association and (ii) multiple drug binding sites, each with a defined specificity. 

The quest to determine whether P-gp contains multiple drug binding sites employed a number of distinct approaches. For example, site-directed mutagenesis revealed a multitude of residues that when mutated could alter the pattern of drug resistance conferred by P-gp [183-185]. The effects of mutations on the activity were... 

Fig. 28.19 Multiple drug binding sites on the L-type voltage-gated calcium channel.

To account for the observed broad substrate specificities for both CYP3A4 and P-gp, the presence of multiple drug binding sites has been proposed. The first experimentally determined signs of complex kinetic... 

Pharmacol., 58, 624 (2000). Communication between Multiple Drug Binding Sites on P-Glycoprotein. 

Ni Q., Xu H., Partilla J., Costa B.D., Rice K., Rothman R. Selective labeling of K2 opioid receptors in rat brain by [125I]IOXY interactions of opioid peptides and other drugs with multiple K2a binding sites. Peptides. 14 1279, 1993. 

Chadwick, C.C., Krafte, D.S., Oconnor, B., Volberg, W.A., Ezrin, A.M., Johnson, R.E. and Silver, P.J. (1995) Evidence for multiple antiarrhythmic binding-sites on the cardiac rapidly activating delayed rectifier K - - channel. Drug Development Research, 34, 376-380. 

An important characteristic of both classes of ion channel is that they possess multiple diug binding sites. Many of the channel-active drugs have achieved particular therapeutic importance, including, for example, the Ca2+ antagonises, widely used for a number of cardiovascular disorders, such as hypertension. 

They are multiple pharmacologic receptors, each channel typically possessing several specific drug binding sites... 

A variety of pharmaceutical drugs or intermediates, such as -blockers, P-agonists, benzodiazepines, nonsteroidal anti-inflammatory drugs, and sulfoxides, can be enantioresolved on the same polysaccharide CSP in all HPLC separation modes and in SFC. A common structural feature of these compounds is that they all contain at least one aromatic group and multiple hydrogen-binding sites in... 

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