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Protein-Targeted Glycan Editing on Living Cells Disrupts KRAS Signaling.
Li, Yiran; Huo, Fan; Chen, Liusheng; Wang, Haiqi; Wu, Jianzhuang; Zhang, Peiwen; Feng, Nan; Li, Wei; Wang, Lan; Wang, Yichun; Wang, Xiaojian; Yang, Xiaoliang; Lu, Zhiqiang; Mao, Yang; Yan, Chao; Ding, Lin; Ju, Huangxian.
Affiliation
  • Li Y; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Huo F; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 210023, Nanjing, P. R. China.
  • Chen L; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Wang H; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Wu J; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 210023, Nanjing, P. R. China.
  • Zhang P; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Feng N; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Li W; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Wang L; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Wang Y; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Wang X; Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, 211816, Nanjing, P. R. China.
  • Yang X; State Key Laboratory of Coordination Chemistry and Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
  • Lu Z; College of Chemistry and Chemical Engineering and Henan Key Laboratory of Function-Oriented Porous Materials, Luo-yang Normal University, 471934, Luoyang, P. R. China.
  • Mao Y; School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, P. R. China.
  • Yan C; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 210023, Nanjing, P. R. China.
  • Ding L; Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, 210023, Nanjing, P. R. China.
  • Ju H; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, P. R. China.
Angew Chem Int Ed Engl ; 62(26): e202218148, 2023 06 26.
Article in En | MEDLINE | ID: mdl-37103924
The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proto-Oncogene Proteins p21(ras) / Lung Neoplasms Limits: Humans Language: En Journal: Angew Chem Int Ed Engl Year: 2023 Document type: Article Country of publication: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proto-Oncogene Proteins p21(ras) / Lung Neoplasms Limits: Humans Language: En Journal: Angew Chem Int Ed Engl Year: 2023 Document type: Article Country of publication: Germany