Loading...
Total synthesis and evaluation of 22-(3-azidobenzoyloxy)methyl epothilone C for photoaffinity labeling of β-tubulin
Hutt, Oliver E. ; Inagaki, Jun ; Reddy, Bollu S. ; Nair, Sajiv K. ; Reiff, Emily A. ; Henri, John T. ; Greiner, Jack F. ; VanderVelde, David G. ; Chiu, Ting-Lan ; Amin, Elizabeth A. ... show 2 more
Hutt, Oliver E.
Inagaki, Jun
Reddy, Bollu S.
Nair, Sajiv K.
Reiff, Emily A.
Henri, John T.
Greiner, Jack F.
VanderVelde, David G.
Chiu, Ting-Lan
Amin, Elizabeth A.
Citations
Altmetric:
Abstract
The total synthesis of 22-(3-azidobenzoyloxy)methyl epothilone C is described as a potential photoaffinity probe to elucidate the β-tubulin binding site. A sequential Suzuki-aldol-Yamaguchi macrolactonization strategy was utilized employing a novel derivatized C1–C6 fragment. The C22-functionalized analog exhibited good activity in microtubule assembly assays, but cytotoxicity was significantly reduced. Molecular modeling simulations indicated that excessive steric bulk in the C22 position is accommodated by the large hydrophobic pocket of the binding site. Photoaffinity labeling studies were inconclusive suggesting non-specific labeling.
Description
Date
2009-06-15
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
Epothilone, Photoaffinity labels, Microtubules
Citation
Hutt, O. E., Inagaki, J., Reddy, B. S., Nair, S. K., Reiff, E. A., Henri, J. T., … Georg, G. I. (2009). Total synthesis and evaluation of 22-(3-azidobenzoyloxy)methyl epothilone C for photoaffinity labeling of β-tubulin. Bioorganic & Medicinal Chemistry Letters, 19(12), 3293–3296. http://doi.org/10.1016/j.bmcl.2009.04.077