Chemoenzymatic Synthesis of Highly <i>O</i> ‐Glycosylated MUC7 Glycopeptides for Probing Inhibitory Activity against <i>Pseudomonas aeruginosa</i> Biofilm Formation
MUC7, a highly glycosylated protein in saliva and respiratory tract, plays potential roles in facilitating bacterial clearance and preventing microbial invasion. The complexity of glycan structures and multiplicity of glycosylation sites of MUC7 make it very difficult to explore accurate biofunctions against pathogens. Here, we report an efficiently convergent chemoenzymatic approach to firstly synthesize highly O-glycosylated MUC7 glycopeptides with nine glycosylation sites bearing various glycoforms via the combined use of hydrophobic tag-assisted liquid-phase peptide synthesis and enzymatic-catalyzed glycan elongation. Biological evaluations reveal that different glycoforms of synthetic MUC7 glycopeptides mediate unique activities against biofilm formation of Pseudomonas aeruginosa, among which sialylated MUC7 glycopeptide exhibits better inhibitory activity and has the potential to develop antibacterial drugs.
Authors
- Zhengwei Huang (ORCID: https://orcid.org/0000-0001-7973-5269)
- Yukun Jiang (ORCID: https://orcid.org/0000-0002-4139-3600)
- Tiehai Li (ORCID: https://orcid.org/0000-0002-3600-1828)
- Lefu Lan (ORCID: https://orcid.org/0000-0002-5551-5496)
- Tianhui Hao
- Huan Liu (ORCID: https://orcid.org/0000-0002-2253-9176)
- Zhonghua Li (ORCID: https://orcid.org/0000-0002-7625-7043)
- Qi Du
- Wenjing Ma (ORCID: https://orcid.org/0009-0001-8457-5412)
- Junyuan Luo
Institutions
- Shanghai Jiao Tong University (CN)
- Anhui Medical University (CN)
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Shanghai Stomatological Hospital (CN)
- Shanghai Ninth People's Hospital (CN)
- Shanghai Institute of Materia Medica (CN)
- Zero to Three (US)
- Zhongshan Hospital (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1002/anie.202424312
- Citations
- 5
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Science and Technology Commission of Shanghai Municipality
- University of Chinese Academy of Sciences
- National Key Research and Development Program of China