Abstract
Saponins are triterpene glycoside natural products that exhibit many different biological properties, including activation and modulation of the immune system, and have therefore attracted significant interest as immunological adjuvants for use in vaccines. QS-21 is the most widely used and promising saponin adjuvant but suffers from several liabilities, such as scarcity, dose-limiting toxicity, and hydrolytic instability. Chemical synthesis has emerged as a powerful approach to obtain homogeneous, pure samples of QS-21 and to improve its properties and therapeutic profile by providing access to optimized, synthetic saponin variants. Herein, we describe a general method for the semisynthesis of these molecules from QS-21, with detailed synthetic protocols for two saponin variants developed in our recent work.
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Acknowledgements
Dedicated to the memory of our mentor and colleague, Professor David Y. Gin (1967–2011). We thank Dr. George Sukenick, Rong Wang, Dr. Hui Liu, Hui Fang, and Dr. Sylvi Rusli (MSKCC) for expert mass spectral analyses. A. F.-T. thanks the Spanish Ministry of Education (ME–Fulbright postdoctoral fellowship) and the European Commission (Marie Curie Individual Fellowship) for postdoctoral funding. Financial support from the NIH (R01 AI085622 to D. Y. G., R01 GM058833 to D. S. T. and D. Y. G., and P30 CA008748 to C. B. Thompson), William and Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the MSKCC Center for Experimental Therapeutics is gratefully acknowledged.
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Fernández-Tejada, A., Walkowicz, W.E., Tan, D.S., Gin, D.Y. (2017). Semisynthesis of Analogues of the Saponin Immunoadjuvant QS-21. In: Fox, C. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 1494. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6445-1_4
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DOI: https://doi.org/10.1007/978-1-4939-6445-1_4
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