Generation of a novel anti-geldanamycin antibody.
Geldanamycin (GA) and herbimycin A are benzoquinone ansamycins (BAs) that inhibit the molecular chaperone HSP90. The central role of HSP90 in maintaining the conformation, stability, and function of key oncogenic proteins involved in signal transduction pathways renders BAs attractive candidates for clinical development. Two GA derivatives, 17-allylamino-17-demethoxygeldanamycin and 17-demethoxy-17-N,N-dimethylaminoethylamino-geldanamycin are currently evaluated in clinical trials. The present study demonstrates generation of a polyclonal antibody elicited against GA that was conjugated to keyhole limpet hemocyanin via its 17 position. The anti-GA antibody recognizes GA as well as other BAs, suggesting its possible application for monitoring plasma levels of GA derivatives. The specificity of the antibody towards BAs is demonstrated by its inability to recognize radicicol, an HSP90 inhibitor not related to BAs. This antibody thus presents a novel research tool as well as a possible alternative approach for monitoring drug levels in patients.
Barzilay
Eran
E
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel.
Ben-Califa
Nathalie
N
Shahar
Mika
M
Kashman
Yoel
Y
Neumann
Drorit
D
D000906:Antibodies / Q000276:immunology*; D016227:Benzoquinones / Q000737:chemistry; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D007769:Lactams / Q000737:chemistry; D047029:Lactams, Macrocyclic; D011809:Quinones / Q000737:chemistry / Q000276:immunology*
C500884:17-hexamethylenediamine-17-demethoxygeldanamycin; D000906:Antibodies; D016227:Benzoquinones; D007769:Lactams; D047029:Lactams, Macrocyclic; D011809:Quinones; C001277:geldanamycin