Chemoenzymatic Synthesis of Glycopeptide Library Decodes Sialylation-Dependent Immunodominance to Enable a Potent Multicomponent Antitumor Vaccine
文献类型：期刊论文
| 作者 | Wu, Ye4,5; Ma, Wenjing5; Jiang, Yinyu5; Li, Xiaoyu4; Ling, Yi4; Guo, Yajing4; Zhou, Yang2,4; Liu, Bingyuan4; Huang, Hongxia4; Hong, Sheng4 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2026-01-19 |
| 页码 | 15 |
| 关键词 | Antitumor immunity Carbohydrates Glycopeptide synthesis Glycopeptide vaccines Vaccine design |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202525026 |
| 通讯作者 | Cai, Hui(caihui5@mail.sysu.edu.cn) ; Li, Tiehai(tiehaili@simm.ac.cn) |
| 英文摘要 | Aberrant sialylation is a hallmark of tumor glycosylation that promotes malignant progression and immune evasion. While sialylated carbohydrates represent attractive targets for anticancer vaccines, structural and antigenic insights into glycopeptides are still hampered by limited access to well-defined structures, rendering their immunogenicity unclear. Herein, we describe an efficient chemoenzymatic platform for facile synthesis of a glycopeptide library comprising 18 structures with diverse O-glycans at different glycosylation sites. Glycopeptide microarray-based serological screening revealed a consistent preference of cancer patient sera for sialylated glycopeptides over their non-sialylated counterparts. Motivated by this finding, we performed systematic immunological evaluations of sialylated and non-sialylated glycopeptide-tetanus toxoid (TT) conjugates, demonstrating that sialylated glycopeptide-TT conjugates elicit stronger antibody responses, enhanced tumor cell recognition, and more potent tumor growth inhibition through synergistic activation of antigen-presenting cells and T cell subsets. Furthermore, we developed a multicomponent cocktail vaccine by incorporating four sialylated glycopeptides, which elicited broader and more potent immune activation than single-antigen formulations. Antisera from the cocktail vaccine exhibited strong binding to human tumor tissues, underscoring the clinical relevance of our findings. This work establishes sialylation as a key determinant of glycopeptide immunogenicity and provides a rational strategy for developing next-generation glycopeptide-based cancer vaccines. |
| WOS关键词 | SOLID-PHASE SYNTHESIS ; ANTIBODY-RESPONSE ; BREAST-CANCER ; MUC1 ; GLYCOSYLATION ; STRATEGIES ; CANDIDATE ; MELANOMA ; PROSTATE ; ELICIT |
| 资助项目 | Shenzhen Medical Research Fund[B2402031] ; The Pearl River Talent Plan Innovation and Entrepreneurship Team Project of Guangdong Province[2021ZT09Y544] ; National Natural Science Foundation of China[22377134] ; National Natural Science Foundation of China[22277150] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1060000] ; Shenzhen Science and Technology Program[JCYJ20220818102005011] ; Guangdong ST Program[2024B1111160003] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001664054700001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322685]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Cai, Hui; Li, Tiehai |
| 作者单位 | 1.Peoples Hosp Longhua, Dept Urol, Shenzhen 518109, Guangdong, Peoples R China 2.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China 3.Sun Yat Sen Univ, Affiliated Hosp 8, Shenzhen 518033, Guangdong, Peoples R China 4.Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Shenzhen Campus, Shenzhen 518107, Guangdong, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Ye,Ma, Wenjing,Jiang, Yinyu,et al. Chemoenzymatic Synthesis of Glycopeptide Library Decodes Sialylation-Dependent Immunodominance to Enable a Potent Multicomponent Antitumor Vaccine[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2026:15. |
| APA | Wu, Ye.,Ma, Wenjing.,Jiang, Yinyu.,Li, Xiaoyu.,Ling, Yi.,...&Li, Tiehai.(2026).Chemoenzymatic Synthesis of Glycopeptide Library Decodes Sialylation-Dependent Immunodominance to Enable a Potent Multicomponent Antitumor Vaccine.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,15. |
| MLA | Wu, Ye,et al."Chemoenzymatic Synthesis of Glycopeptide Library Decodes Sialylation-Dependent Immunodominance to Enable a Potent Multicomponent Antitumor Vaccine".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2026):15. |
入库方式： OAI收割
来源：上海药物研究所
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