A. Demmer et al., Iodomycin and iodipine, a structural analogue of azidopine, bind to a common domain in hamster P-glycoprotein, EUR J BIOCH, 264(3), 1999, pp. 800-805
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.