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

Publication ,  Journal Article
Pang, Y; Liu, J; Qi, Y; Li, X; Chilkoti, A
Published in: Angewandte Chemie (International ed. in English)
August 2016

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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Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

August 2016

Volume

55

Issue

35

Start / End Page

10296 / 10300

Related Subject Headings

  • Polyethylene Glycols
  • Peptides
  • Organic Chemistry
  • Molecular Structure
  • Green Fluorescent Proteins
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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ICMJE
MLA
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Pang, Y., Liu, J., Qi, Y., Li, X., & Chilkoti, A. (2016). A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics. Angewandte Chemie (International Ed. in English), 55(35), 10296–10300. https://doi.org/10.1002/anie.201604661
Pang, Yan, Jinyao Liu, Yizhi Qi, Xinghai Li, and Ashutosh Chilkoti. “A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.Angewandte Chemie (International Ed. in English) 55, no. 35 (August 2016): 10296–300. https://doi.org/10.1002/anie.201604661.
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). 2016 Aug;55(35):10296–300.
Pang, Yan, et al. “A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.Angewandte Chemie (International Ed. in English), vol. 55, no. 35, Aug. 2016, pp. 10296–300. Epmc, doi:10.1002/anie.201604661.
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). 2016 Aug;55(35):10296–10300.
Journal cover image

Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

August 2016

Volume

55

Issue

35

Start / End Page

10296 / 10300

Related Subject Headings

  • Polyethylene Glycols
  • Peptides
  • Organic Chemistry
  • Molecular Structure
  • Green Fluorescent Proteins
  • 34 Chemical sciences
  • 03 Chemical Sciences