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 multidrug resistance, one major cause of the failure of cancer chemotherapy in humans. This study reports that [125I]iodipine, a structural analogue of the 1,4-dihydropyridine azidopine, shares a common binding site with iodomycin, a Bolton-Hunter derivative of the anthracycline daunomycin. This binding site is different from that described for iodoarylazidoprazosin, which is presumed to share a common binding site with azidopine. Edman sequencing revealed that [125I]iodipine had photolabelled the same peptide as iodomycin and spans the primary sequence of hamster isoform pgp1 from amino acid 230 to amino acid 312.
Demmer
A
A
Klinische Forschergruppe, Zentrum Biochemie, Medizinische Hochschule, Hannover, Germany. Demmer.annette@MH-Hannover.de
Andreae
S
S
Thole
H
H
Tümmler
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000378:metabolism*; D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004095:Dihydropyridines / Q000737:chemistry / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000737:chemistry / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides; D004095:Dihydropyridines; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C060588:iodomycin; C041130:azidopine; C041028:iodipine; D003630:Daunorubicin