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Zwitterionic Peptide Cloak Mimics Protein Surfaces for Protein Protection
Author(s) -
Yuan Zhefan,
Li Bowen,
Niu Liqian,
Tang Chenjue,
McMullen Patrick,
Jain Priyesh,
He Yuwei,
Jiang Shaoyi
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202004995
Subject(s) - immunogenicity , lysine , cloak , peptide , amino acid , in vivo , chemistry , combinatorial chemistry , glutamic acid , nanotechnology , biochemistry , materials science , biology , metamaterial , antibody , immunology , microbiology and biotechnology , optoelectronics
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.