SYNTHESIS OF QUILLAJA SAPONINS DERIVED FROM QS-21. DEFINING KEY STRUCTURAL ELEMENTS IN THE DESIGN OF SIMPLIFIED VACCINE ADJUVANTS AND BIOCHEMICAL PROBES

Alberto Fernandez-Tejada 1 Eric Chea 1 Constantine George 2 Govind Ragupathi 2 David Gin 1
1Department of Molecular Pharmacology and Chemistry, Sloan-Kettering Institute for Cancer Research, New York, NY
2Department of Medicine, Sloan-Kettering Institute for Cancer Research, New York, NY
QS-21 is one of the most promising immunoadjuvants currently undergoing clinical and preclinical investigation for use with a wide range of vaccines to treat cancer, malaria, HIV and Alzheimer's disease. However, it suffers from several liabilities, including limited access from the natural source, chemical instability during storage, low-grade toxic side effects, and an unknown mechanism of action. Herein, we report the design, synthesis and immunological evaluation of simplified QS-21 variants to assess key structural requirements for adjuvant activity. This structure-function exploration has provided practical access to saponin probes as chemical tools for mechanistic investigation and has enabled the identification of novel, potential alternatives to the clinical use of QS-21.

 
Chemical structure of the saponin adjuvant QS-21







 




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