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Polypeptides with High Zwitterion Density for Safe and Effective Therapeutics
Author(s) -
Zhang Peng,
Jain Priyesh,
Tsao Caroline,
Yuan Zhefan,
Li Wenchen,
Li Bowen,
Wu Kan,
Hung HsiangChieh,
Lin Xiaojie,
Jiang Shaoyi
Publication year - 2018
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.201802452
Subject(s) - immunogenicity , zwitterion , peg ratio , pharmacokinetics , ethylene glycol , pharmacology , chemistry , biodistribution , immune system , kidney , antibody , medicine , biochemistry , immunology , in vitro , organic chemistry , finance , molecule , economics
The commonly used “stealth material” poly(ethylene glycol) (PEG) effectively promotes the pharmacokinetics of therapeutic cargos while reducing their immune response. However, recent studies have suggested that PEG could induce adverse reactions, including the emergence of anti‐PEG antibodies and tissue histologic changes. An alternative stealth material with no or less immunogenicity and organ toxicity is thus urgently needed. We designed a polypeptide with high zwitterion density (PepCB) as a stealth material for therapeutics. Neither tissue histological changes in liver, kidney, or spleen, nor abnormal behavior, sickness or death was induced by the synthesized polymer after high‐dosage administration for three months in rats. When conjugated to a therapeutic protein uricase, the uricase–PepCB bioconjugate showed significantly improved pharmacokinetics and immunological properties compared with uricase–PEG conjugates.