Total Synthesis of Cryptophycin A and Analogs
Annual rept. 16 Mar 1999-15 Mar 2000
KANSAS UNIV LAWRENCE
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Cryptophycins are antimitotic metabolites isolated from an algae. By interacting with tubulin, Cryptophycin A induces apoptosis. Preliminary in vivo studies showed that the cryptophycins are active against breast tumors. To date, structure-activity relationship studies regarding the C3 and ClO side chains have not been fully probed. The synthesis of the epi-C3 cryptophycin analogues has been completed. Scale-up of the synthesis is underway so full characterization and the biological testing can be completed. The total synthesis of the ClO analogue containing the C3 chloro group, derived from the substitution of the D-3-chlorophenylalanine for the D-tyrosine moiety, is nearly complete. In vitro biological testing will be performed to determine biological activity in selected breast cancer cell lines and in a tubulin assay. The studies outlined in this research summary will provide insight into how cryptophycin and tubulin interact. Information obtained about the binding site and where cryptophycin binds to tubulin will help reveal how the potent cytotoxic effects are exerted in cancerous cells. This may inturn help scientists better understand tubulins structure so that more potent anticancer agents can be prepared in the future.
- Anatomy and Physiology
- Medicine and Medical Research