Click conjugation of trivalent mannosyl glycocluster with human serum albumin to generate a cell targeting delivery vehicle

Yu Fan Zhou; Hui Xu; Dan-Yang Chen; Xi Le Hu; Guo-Rong Chen; Tony James; Xiao-Peng He

doi:10.1016/j.bmc.2025.118335

Click conjugation of trivalent mannosyl glycocluster with human serum albumin to generate a cell targeting delivery vehicle

Yu Fan Zhou, Hui Xu, Dan-Yang Chen, Xi Le Hu, Guo-Rong Chen, Tony James, Xiao-Peng He

Research output: Contribution to journal › Article › peer-review

Abstract

The exploitation of glycans as targeting agents to construct delivery materials has proved useful for targeted disease diagnosis and therapy. To achieve effective targeting, multivalent glycosides are prepared to enhance avidity with sugar receptors. In this study, we designed and synthesized a new trivalent mannoside (Man3-PEG3-N3) bearing an azido unit. This azido mannosyl glycocluster was used to conjugate with cyclooctyne-modified human serum albumin (HSA) through strain-promoted click chemistry. Mass spectroscopic analysis validated the successful construction of the glycocluster-conjugated HSA, and a fluorescence titration assay indicated that the resulting conjugate is capable of accommodating an environmentally sensitive dye.

Original language	English
Article number	118335
Journal	Bioorganic & Medicinal Chemistry
Volume	129
Early online date	29 Jul 2025
DOIs	https://doi.org/10.1016/j.bmc.2025.118335
Publication status	Published - 1 Nov 2025

Data Availability Statement

The data supporting this article are included as part of the ESI.

Acknowledgements

The Research Center of Analysis and Test of East China University of Science and Technology was gratefully acknowledged for assistance in analytical experiments.

Funding

The authors thank the Natural National Science Foundation of China (NSFC) (Nos. 92253306, 82130099 and 22477030), Science and Technology Commission of Shanghai Municipality (grant No. 24DX1400200), the International Cooperation Program of Shanghai Science and Technology (No. 23490711600), the Fundamental Research Funds for the Central Universities (222201717003), the Programme of Introducing Talents of Discipline to Universities (B16017), the National Natural Science Foundation of Shanghai Science and Technology (No. 24ZR1415400), the Shanghai Oriental Talents youth Program (No. QNKJ2024010), the Shanghai Xuhui District Hospital Local Cooperation Project (23XHYD-20), the Open Funding Project of the State Key Laboratory of Fine Chemicals, Dalian University of Technology (KF 2402), State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, P. R. China, Ministry of Education Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer (Naval Medical University) (Grant 2023-MEKLLC-MS/ZD-00*) and Shandong Laboratory Program (SYS202205) for financial support. The Research Center of Analysis and Test of East China University of Science and Technology was gratefully acknowledged for assistance in analytical experiments. T.D.J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support.

Funders	Funder number
State Key Laboratory of Catalysis
Ministry of Education Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer
University of Bath
State Key Laboratory of Fine Chemicals
Biosensing and Chemometrics, Hunan University	410082
National Natural Science Foundation of China	82130099, 22477030, 92253306
Shanghai Xuhui District Hospital	23XHYD-20
Shanghai Science and Technology Development Foundation	24ZR1415400
Shandong Laboratory Program	SYS202205
Dalian University of Technology	KF 2402
International Science and Technology Cooperation Programme	23490711600
Shanghai Oriental Talents youth Program	QNKJ2024010
Project 211	B16017
Naval Medical University	2023-MEKLLC-MS/ZD-00*
Fundamental Research Funds for the Central Universities	222201717003
Science and Technology Commission of Shanghai Municipality	24DX1400200
Henan Normal University	2020ZD01

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Click chemistry
Fluorescence
Glycocluster
Human serum albumin
Multivalency

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Organic Chemistry
Clinical Biochemistry

Access to Document

10.1016/j.bmc.2025.118335Licence: CC BY

Cite this

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abstract = "The exploitation of glycans as targeting agents to construct delivery materials has proved useful for targeted disease diagnosis and therapy. To achieve effective targeting, multivalent glycosides are prepared to enhance avidity with sugar receptors. In this study, we designed and synthesized a new trivalent mannoside (Man3-PEG3-N3) bearing an azido unit. This azido mannosyl glycocluster was used to conjugate with cyclooctyne-modified human serum albumin (HSA) through strain-promoted click chemistry. Mass spectroscopic analysis validated the successful construction of the glycocluster-conjugated HSA, and a fluorescence titration assay indicated that the resulting conjugate is capable of accommodating an environmentally sensitive dye.",

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AU - Zhou, Yu Fan

AU - Xu, Hui

AU - Chen, Dan-Yang

AU - Hu, Xi Le

AU - Chen, Guo-Rong

AU - James, Tony

AU - He, Xiao-Peng

PY - 2025/11/1

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AB - The exploitation of glycans as targeting agents to construct delivery materials has proved useful for targeted disease diagnosis and therapy. To achieve effective targeting, multivalent glycosides are prepared to enhance avidity with sugar receptors. In this study, we designed and synthesized a new trivalent mannoside (Man3-PEG3-N3) bearing an azido unit. This azido mannosyl glycocluster was used to conjugate with cyclooctyne-modified human serum albumin (HSA) through strain-promoted click chemistry. Mass spectroscopic analysis validated the successful construction of the glycocluster-conjugated HSA, and a fluorescence titration assay indicated that the resulting conjugate is capable of accommodating an environmentally sensitive dye.

KW - Click chemistry

KW - Fluorescence

KW - Glycocluster

KW - Human serum albumin

KW - Multivalency

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DO - 10.1016/j.bmc.2025.118335

M3 - Article

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VL - 129

JO - Bioorganic & Medicinal Chemistry

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Click conjugation of trivalent mannosyl glycocluster with human serum albumin to generate a cell targeting delivery vehicle

Abstract

Data Availability Statement

Acknowledgements

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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