Structure-Activity Relationship Study of Momordica Saponin II Derivatives as Vaccine Adjuvants.
Structure-Activity Relationship Study of Momordica Saponin II Derivatives as Vaccine Adjuvants.
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DOI：
10.1021/acs.jmedchem.2c01087
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发表时间：
2022-11-10
影响因子：
7.3
通讯作者：
Wang, Pengfei
中科院分区：
文献类型：
--
作者：
Kim, Hyunjung;Bai, Di;Ghosh, Sadashib;Franks, Michael L.;Wang, Xifeng;Yan, Cheng;Liu, Zheng;Zhang, Ping;Michalek, Suzanne M.;Leavenworth, Jianmei W.;Wang, Pengfei
VSA-2是一种新开发的半合成皂苷免疫刺激剂。从多年生植物Momordica cochinchinensis春中分离的Momordica saponin II (MS II)，在其C3位置的支链三糖结构域上加入末端功能化侧链制备了该化合物。VSA-2与临床证实的皂苷佐剂QS-21的直接比较表明，VSA-2在增强体液和细胞免疫应答方面与QS-21相当。构效关系研究表明，侧链的结构变化对皂苷的佐剂活性有显著影响。然而，由于VSA-2分子框架完整，新的VSA-2类似物在侧链末端苯基上具有各种取代，保留了增强抗原特异性体液和细胞反应的能力。
VSA-2 is a recently developed semisynthetic saponin immunostimulant. It is prepared by incorporating a terminal-functionalized side chain to the branched trisaccharide domain at the C3 position of Momordica saponin II (MS II) isolated from the seeds of perennial Momordica cochinchinensis Spreng. Direct comparison of VSA-2 and the clinically proven saponin adjuvant QS-21 shows that VSA-2 is comparable to QS-21 in enhancing humoral and cellular immune responses. Structure–activity relationship studies show that structural changes in the side chain have a significant impact on saponins’ adjuvant activity. However, with the VSA-2 molecular framework intact, the new VSA-2 analogues with various substitution(s) at the terminal benzyl group of the side chain retain the ability of potentiating antigen-specific humoral and cellular responses.
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