title: Semisynthesis of Analogues of the Saponin Immunoadjuvant QS-21.
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.
authors.affiliation: Chemical Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. alberto.fernandezt@gmail.com.|Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road 12, OX1 3TA, Oxford, UK. alberto.fernandezt@gmail.com.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Tejada
authors.affiliation: Chemical Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Walkowicz
authors.affiliation: Chemical Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. tand@mskcc.org.|Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. tand@mskcc.org.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Chemical Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.|Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Gin
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry*; D031990:Quillaja / Q000737:chemistry*; D012503:Saponins / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D012503:Saponins
keywords: Carbohydrate; Glycosylation; Immunoadjuvant; Natural product; QS-21; Saponin; Semisynthesis; Vaccine