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- Title
Polypeptides with High Zwitterion Density for Safe and Effective Therapeutics.
- Authors
Zhang, Peng; Jain, Priyesh; Tsao, Caroline; Yuan, Zhefan; Li, Wenchen; Wu, Kan; Hung, Hsiang‐Chieh; Lin, Xiaojie; Jiang, Shaoyi; Li, Bowen
- Abstract
Abstract: 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.
- Subjects
POLYPEPTIDES; ZWITTERIONS; PROPARGYL alcohol; TRIMETHYLSILYL compounds; DISULFIDES
- Publication
Angewandte Chemie, 2018, Vol 130, Issue 26, p7869
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201802452