Elsevier

Biochemical Pharmacology

Volume 43, Issue 1, 9 January 1992, Pages 89-93
Biochemical Pharmacology

Photoaffinity substrates for P-glycoprotein

https://doi.org/10.1016/0006-2952(92)90665-6Get rights and content

Abstract

A variety of compounds can inhibit the function of P-glycoprotein (Pgp) by binding to it and preventing the efflux of anticancer drug substrates. While the molecular architecture of the drug binding site(s) in Pgp is not known, it is clear that modulators in general appear to conform to some general physical-chemical rules. In this paper, we discuss the basic concepts of drug recognition by Pgp as currently understood. We also examine the compounds used to photoaffinity label this protein and discuss their utility in identifying drug binding sites. Finally, we show that a photoaffinity analog of daunorubicin, [3H]azidobenzoyl-daunorubicin ([3H]AB-DNR), is a good affinity labeling reagent for Pgp. A finding of interest is that vinblastine and verapamil compete more effectively than daunorubicin for [3H]AB-DNR binding to Pgp, suggesting that vinblastine and verpamil have similar structural features not shared by daunorubicin.

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    Present address: BASF Bioresearch Corporation, 195 Albany Street, Cambridge, MA 02139, U.S.A.

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