Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety
文献类型：期刊论文
| 作者 | Hao, Tianhui4,5; Mi, Tian5; Chu, Qinyu2,3,4; Ma, Wenjing4,5; Cheng, Xi2,3,4; Zang, Yi1; Li, Jia2,4,5 ; Li, Tiehai4,5
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| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2024-06-05 |
| 页码 | 7 |
| 关键词 | Glycolipid KRN7000 stereospecific alpha-galactosylation Th1/Th2 cytokines molecular docking |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.4c00199 |
| 通讯作者 | Cheng, Xi(xicheng@simm.ac.cn) ; Zang, Yi(yzang@lglab.ac.cn) ; Li, Jia(jli@simm.ac.cn) ; Li, Tiehai(tiehaili@simm.ac.cn) |
| 英文摘要 | alpha-Galactosylceramide (KRN7000 or alpha-GalCer) analogues terminated with phenyl (Ph) groups at the acyl moiety possess more potency than KRN7000 to activate invariant natural killer T (iNKT) cells for inducing a T helper 1 (Th1)-biased immune response. However, biological activities of phenyl glycolipids with thio-modifications at the acyl moiety remain unknown, and facile approaches for highly stereoselective synthesis of KRN7000 and its analogues are rather scarce. Herein, we exploited 4,6-di-O-tert-butylsilylene (DTBS)-directed stereospecific galactosylation to efficiently synthesize various alpha-GalCer analogues bearing thioamide, terminal thiophenyl and dual modifications at the acyl moiety. Biological evaluations suggest that a new analogue S34 featuring a terminal Ph-S-Ph-F group exhibits a more superior Th1-biased immune response in mice. Molecular docking analysis revealed that the introduction of a sulfur atom influences vital hydrogen bonding interactions between glycolipids and the cluster of differentiation 1d (CDld), thus adjusting the stability of the glycolipid-CDld complex. |
| WOS关键词 | KILLER T-CELLS ; ALPHA-GALACTOSYL CERAMIDE ; GLYCOSYL IODIDE ; ACTIVATION ; ADJUVANT ; RECOGNITION ; GLYCOLIPIDS ; DISCOVERY ; RESPONSES ; AGONIST |
| 资助项目 | National Natural Science Foundation of China[22077130] ; National Natural Science Foundation of China[22377134] ; National Natural Science Foundation of China[82130099] ; National Natural Science Foundation of China[TM202301H002] ; Shanghai Municipal Science Technology Major Project[SIMM0120232001] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[2021YFA1301900] ; Shanghai Municipal Science Technology Major Project, National Key Research and Development Program of China[2022077] ; Fund of Youth Innovation Promotion Association |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001242818300001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311603]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cheng, Xi; Zang, Yi; Li, Jia; Li, Tiehai |
| 作者单位 | 1.Lingang Lab, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hao, Tianhui,Mi, Tian,Chu, Qinyu,et al. Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety[J]. ACS MEDICINAL CHEMISTRY LETTERS,2024:7. |
| APA | Hao, Tianhui.,Mi, Tian.,Chu, Qinyu.,Ma, Wenjing.,Cheng, Xi.,...&Li, Tiehai.(2024).Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety.ACS MEDICINAL CHEMISTRY LETTERS,7. |
| MLA | Hao, Tianhui,et al."Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety".ACS MEDICINAL CHEMISTRY LETTERS (2024):7. |
入库方式： OAI收割
来源：上海药物研究所
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