Synthesis and binding properties of photoactivable biotin-conjugated verapamil derivatives for the study of P-170 glycoprotein.
The design and synthesis of two photoactivable biotin-labeled analogues of verapamil (6 and 7) is reported. Preliminary evaluation of the biological profile of 6 (EDP 137) and 7 (EDP 141) shows that they have comparable affinities to that of verapamil for P-170, the protein responsible for multidrug resistance (MDR). Since both appear to bind irreversibly to the protein and the presence of biotin in their structure makes them easily detectable by avidin, they promise to be of great help in studying the protein and its mechanism of action.
Teodori
E
E
Dipartimento di Scienze Farmaceutiche, Universita' di Firenze, Italy.
Ettori
D
D
Garnier-Suillerot
A
A
Gualtieri
F
F
Manetti
D
D
Romanelli
M N
MN
Scapecchi
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D001710:Biotin / Q000737:chemistry*; D006801:Humans; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D010777:Photochemistry; D013055:Spectrophotometry, Infrared; D014700:Verapamil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015335:Molecular Probes; D001710:Biotin; D014700:Verapamil