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

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

• 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.
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