publications by Ashutosh Chilkoti.


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Papers Published

  1. Pang, Y; Liu, J; Qi, Y; Li, X; Chilkoti, A, A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics., Angewandte Chemie (International ed. in English), vol. 55 no. 35 (August, 2016), pp. 10296-10300 [doi] .
    (last updated on 2024/03/29)

    Abstract:
    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.