期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 55, 期 35, 页码 10296-10300出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201604661
关键词
click chemistry; diabetes; pharmacokinetics; prodrugs; protein modification
资金
- National Institutes of Health [R01-DK092665]
A versatile method is described to engineer precisely defined protein/peptide-polymer therapeutics by a modular approach that consists of three steps: 1) fusion of a protein/peptide of interest with an elastin-like polypeptide that enables facile purification and high yields; 2) installation of a clickable group at the C terminus of the recombinant protein/peptide with almost complete conversion by enzyme-mediated ligation; and 3) attachment of a polymer by a click reaction with near-quantitative conversion. We demonstrate that this modular approach is applicable to various protein/peptide drugs and used it to conjugate them to structurally diverse water-soluble polymers that prolong the plasma circulation duration of these proteins. The protein/peptide-polymer conjugates exhibited significantly improved pharmacokinetics and therapeutic effects over the native protein/peptide upon administration to mice. The studies reported here provide a facile method for the synthesis of protein/peptide-polymer conjugates for therapeutic use and other applications.
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