Therapeutic uses of protein-polymer conjugates
A technology of conjugates and uses, applied in the direction of peptide/protein components, animal/human proteins, active ingredients of heterocyclic compounds, etc.
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[0062] Preparation of di-PEG aldehyde
[0063]
[0064] 20kD PEGO(C=O)OSu was prepared from 20kD mPEGOH purchased from (SunBio Inc., CA, USA) according to the method described in Bioconjugate Chem. 1993, 4, 568-569.
[0065] A solution of 6-(1,3-dioxolan-2-yl)hexane-1,5-diamine in dichloromethane (11.97 g solution containing 9.03 mg diamine, 47.8 μmol) was added to a solution containing 20 kD PEGO (C=O)OSu (1.72 g, 86.0 μmol) in a flask. After complete dissolution of PEGO(C=O)OSu, N,N-diisopropylethylamine (79 μL, 478 μmol) was added. The reaction mixture was stirred at room temperature for 24 hours, then methyl tert-butyl ether (200 mL) was added dropwise with stirring. The resulting precipitate was collected and dried under vacuum to yield the bis-PEG acetal (1.69 g, 98%) as a white solid.
[0066] 1 H NMR (400MHz, d 6 -DMSO) δ7.16(t, J=5.2Hz, 1H), 7.06(d, J=8.8Hz, 1H), 4.76(t, J=4.8Hz, 1H), 4.10-3.95(m, 4H), 1.80-1.65 (m, 1H), 1.65-1.50 (m, 1H), 1.48-1.10 (m, 6H)....
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