Iodomycin and iodipine, a structural analogue of azidopine, bind to a common domain in hamster P-glycoprotein

Both the overexpression of P-glycoprotein and the broad range of substrates of this ATP-binding cassette (ABC) transporter induce the phenomenon of mu ltidrug resistance, one major cause of the failure of cancer chemotherapy i n humans. This study reports that [I-125]iodipine, a structural analogue of the 1,4-dihydropyridine azidopine, shares a common binding site with iodom ycin, a Bolton-Hunter derivative of the anthracycline daunomycin. This bind ing site is different from that described for iodoarylazidoprazosin, which is presumed Co share a common binding site with azidopine. Edman sequencing revealed that [I-125]iodipine had photolabelled the same peptide as iodomy cin and spans the primary sequence of hamster isoform pgp1 from amino acid 230 to amino acid 312.