Synthesis of an MUC1 Glycopeptide Dendrimer Based on β-Cyclodextrin by Click Chemistry

Pu-Guang Chen; Zhi-Hua Huang; Zhan-Yi Sun; Qian-Qian Li; Yong-Xiang Chen; Yu-Fen Zhao; Yan-Mei Li

doi:10.1055/s-0036-1590796

Synlett, Table of Contents

Synlett 2017; 28(15): 1961-1965
DOI: 10.1055/s-0036-1590796

cluster

Synthesis of an MUC1 Glycopeptide Dendrimer Based on β-Cyclodextrin by Click Chemistry

Pu-Guang Chen

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Zhi-Hua Huang

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Zhan-Yi Sun

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Qian-Qian Li

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Yong-Xiang Chen

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Yu-Fen Zhao

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

,

Yan-Mei Li*

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. of China Email: liym@mail.tsinghua.edu.cn

› Author Affiliations

Abstract

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Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis

Abstract

Glycopeptide dendrimers are attractive candidates for biomedical applications. Here, an efficient method for preparing multivalent MUC1 glycopeptide dendrimers based on β-cyclodextrin is described. By using copper(I) bromide and thioanisole as a catalyst system, precisely defined heptavalent conjugates were efficiently obtained. Using this heptavalent glycopeptide dendrimer, we observed multivalent effects in recognition and association processes in antibody and epitope interactions, which might have biomedical applications.

Key words

glycopeptide dendrimers - cyclodextrin - copper catalysis - thioanisole - antibody titer - click chemistry

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References

References and Notes

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26 Compound 1; Typical Procedure To a solution of thioanisole (20 μL 166 mol) in DMF (200 μL) was added CuBr (2.1mg, 15.0 μmol) to form a dark-green solution when the CuBr was fully dissolved. A solution of peptide 3 (13 mg; 15.2 μmol) in DMF (0.8 mL) was added to a solution of per-6-azido-β-cyclodextrin (2 mg; 1.5 μmol) in DMF (0.5 mL), and the soln was deoxygenated with N₂ gas. The dark-green catalyst solution was then carefully added to the peptide solution and the mixture was stirred at 65 °C for 2 h. The DMF was removed in vacuo, and the crude product was dissolved in 1:1 H₂O–MeCN (3 mL), purified by RP-HPLC (C18 column), and lyophilized to give a white powder; yield: 7.9 mg (1.1 μmol, 73%). HRMS: m/z [M + H]⁺ calcd for C₃₀₁H₄₇₆N₈₄O₁₂₆: 7284.3422; found (MALDI-TOF) 7285.5317; (ESI ) [M + 4H]⁴⁺ 1823.0, [M + 5H]⁵⁺ 1458.4, [M + 6H]⁶⁺ 1215.7, [M + 7H]⁷⁺ 1042.1.
27 Compound 2 Glycopeptide dendrimer 2 was obtained by a similar procedure to that of peptide dendrimer 1, except that the reaction time was 10 h: yield: 9.4 mg (1.1 μmol, 59%). HRMS: m/z [M + H]⁺calcd for C₃₅₇H₅₆₇N₉₁O₁₆₁: 8705.8978; found: (MALDI-TOF): 8709.4877; (ESI): [M + 5H]⁵⁺ 1743.5, [M + 6H]⁶⁺ 1453.1, [M + 7H]⁷⁺ 1245.5.

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