Zwitterionic Peptide Cloak Mimics Protein Surfaces for Protein Protection

Abstract

Inspired by the amino acid composition of natural protein surfaces, we developed a zwitterionic cloak containing multi‐layers of short alternating glutamic acid and lysine (EK) peptides as a facile, highly effective and low‐immunogenicity approach for the protection and delivery of biotherapeutics. Each EK layer grafted to proteins provides multiple times of new lysine reaction sites for the growth of subsequent EK layers. This unique design allows EK peptides to achieve high coating density on proteins, overcoming the limitation of traditional conjugation strategies that rely on the number of innate lysine groups. A triple‐layer EK cloak manifests to successfully eliminate the specific and non‐specific interactions of protected asparaginase with biological media while prolong the drug circulation time and significantly mitigate its immunogenicity in vivo, suggesting an EK peptide cloak as a promising approach to improve the safety and efficacy of biotherapeutics.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 06, 2020
Source ID
10.1002/anie.202004995

Entities

People

  • Bowen Li
  • Chenjue Tang
  • Liqian Niu
  • Patrick McMullen
  • Priyesh Jain
  • Shaoyi Jiang
  • Yuwei He
  • Zhefan Yuan

Organizations

  • Defense Threat Reduction Agency
  • Fudan University
  • National Institutes of Health
  • University of Washington

Tags

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Nanofabrication and Microfabrication.
  • Nuclear Civil Defense.