Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis of the potent clinical immunoadjuvant QS-21Aapi.

Abstract

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21A(api) in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues.

• Authors: Yong-Jae Kim, Pengfei Wang, Mauricio Navarro-Villalobos, Bridget D Rohde, JohnMark Derryberry, David Y Gin
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 128 Issue 36 Pg. 11906-15 (Sep 13 2006) ISSN: 0002-7863 [Print] United States
• PMID: 16953631 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Sapogenins
• Saponins
• Trisaccharides
• saponin QA-21V1
• quillaic acid
• Oleanolic Acid

Topics

• Adjuvants, Immunologic (chemical synthesis, chemistry)
• Carbohydrate Sequence
• Molecular Sequence Data
• Oleanolic Acid (analogs & derivatives, chemistry)
• Quillaja (chemistry, immunology)
• Sapogenins (chemistry)
• Saponins (chemical synthesis, chemistry)
• Trisaccharides (chemical synthesis, chemistry)