Synthetic studies of complex immunostimulants from Quillaja saponaria: Synthesis of the potent clinical immunoadjuvant QS-21Aapi Journal Article
| Authors: | Kim, Y. J.; Wang, P.; Navarro-Villalobos, M.; Ronde, B. D.; Derryberry, J.; Gin, D. Y. |
| Article Title: | 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-21 Aapi 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. © 2006 American Chemical Society Memorial Sloan-Kettering Cancer Center. |
| Keywords: | unclassified drug; human immunodeficiency virus infection; t lymphocyte; melanoma; breast cancer; drug potency; drug structure; drug synthesis; prostate cancer; lung small cell cancer; immunology; clinical study; cellular immunity; molecular sequence data; tumors; glycosylation; immunological adjuvant; plant extract; immunostimulation; antibodies; vaccine production; adjuvants, immunologic; humoral immunity; diseases; synthesis (chemical); carbohydrate sequence; vaccines; saponins; adjuvants; qs 21; malaria; saponin; quillaja; quillaja saponaria extract; saponin derivative; quillaja saponaria; drug products; drug dosage; immunostimulatory adjuvant; nonnatural saponin; qs 21 a api; immunopotentiation; oleanolic acid; sapogenins; trisaccharides |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 128 |
| Issue: | 36 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2006-09-13 |
| Start Page: | 11906 |
| End Page: | 11915 |
| Language: | English |
| DOI: | 10.1021/ja062364i |
| PUBMED: | 16953631 |
| PROVIDER: | scopus |
| PMCID: | PMC2615099 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 50" - "Export Date: 4 June 2012" - "CODEN: JACSA" - "Source: Scopus" |
