Synthetic studies of complex immunostimulants from Quillaja saponaria:: Synthesis of the potent clinical immunoadjuvant QS-21Aapi
Synthetic studies of complex immunostimulants from Quillaja saponaria:: Synthesis of the potent clinical immunoadjuvant QS-21Aapi
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DOI：
10.1021/ja062364i
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发表时间：
2006-09-13
影响因子：
15
通讯作者：
Gin, David Y.
中科院分区：
文献类型：
--
作者：
Kim, Yong-Jae;Wang, Pengfei;Gin, David Y.
QS-21是疫苗治疗中用于免疫应答增强和剂量节省的最有前途的新佐剂之一，因为其极高水平的效力和其有利的毒性特征。黑色素瘤、乳腺癌、小细胞肺癌、前列腺癌、HIV-1和疟疾是最近和正在进行的80多项疫苗治疗临床试验中针对的众多疾病之一，这些试验涉及QS-21作为增强免疫反应的关键佐剂成分。QS-21是一种天然产物免疫刺激佐剂，以微克剂量引发T细胞和抗体介导的免疫应答。本文报道了以高度模块化策略合成QS-21 A（API），将新型糖基化方法应用于有效皂苷免疫刺激剂的收敛构建。QS-21的化学合成提供了独特的机会，通过制备其他无法获得的非天然皂苷类似物来探索其生物作用模式。
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.