A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Pang, Y; Liu, J; Qi, Y; Li, X; Chilkoti, A

Published Date

  • August 2016

Published In

Volume / Issue

  • 55 / 35

Start / End Page

  • 10296 - 10300

PubMed ID

  • 27439953

Pubmed Central ID

  • 27439953

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201604661


  • eng