title: Synthesis and Evaluation of QS-21-Based Immunoadjuvants with a Terminal-Functionalized Side Chain Incorporated in the West Wing Trisaccharide.
abstract: Three QS-21-based vaccine adjuvant candidates with a terminal-functionalized side chain incorporated in the west wing trisaccharide have been synthesized. The terminal polar functional group serves to increase the solubility of these analogues in water. Two of the synthetic analogues have been shown to have adjuvant activity comparable to that of GPI-0100. The stand-alone adjuvant activity of the new synthetic analogues again confirmed that it is a feasible way to develop new saponin-based vaccine adjuvants through derivatizing at the west wing branched trisaccharide domain. Inclusion of an additional polar functional group such as a carboxyl group (as in 3x) or a monosaccharide (as in 4x and 5x) is sufficient to increase the water solubility of the corresponding synthetic analogues to a level comparable to that of GPI-0100 and suitable for immunological studies and clinical application. The structure of the incorporated side chain has a significant impact on the adjuvant activity in terms of the magnitude and nature of the host's responses.
authors.affiliation: Department of Chemistry, ‡Department of Pediatric Dentistry, and §Department of Microbiology, University of Alabama at Birmingham , 901 14th Street South, Birmingham, Alabama 35294, United States.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Chemistry, ‡Department of Pediatric Dentistry, and §Department of Microbiology, University of Alabama at Birmingham , 901 14th Street South, Birmingham, Alabama 35294, United States.
authors.forename: Dattatray A
authors.initials: DA
authors.lastname: Devalankar
authors.affiliation: Department of Chemistry, ‡Department of Pediatric Dentistry, and §Department of Microbiology, University of Alabama at Birmingham , 901 14th Street South, Birmingham, Alabama 35294, United States.
authors.forename: Qipu
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Chemistry, ‡Department of Pediatric Dentistry, and §Department of Microbiology, University of Alabama at Birmingham , 901 14th Street South, Birmingham, Alabama 35294, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, ‡Department of Pediatric Dentistry, and §Department of Microbiology, University of Alabama at Birmingham , 901 14th Street South, Birmingham, Alabama 35294, United States.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Michalek
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002240:Carbohydrate Sequence; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D066244:Proton Magnetic Resonance Spectroscopy; D012503:Saponins / Q000737:chemistry*; D014312:Trisaccharides / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D012503:Saponins; D014312:Trisaccharides; C078785:saponin QA-21V1