赖氨酸
精氨酸
重组DNA
海兔
毒素
化学
生物化学
生物物理学
药理学
生物
神经科学
氨基酸
基因
作者
Alena M. Wolkersdorfer,Birgit Bergmann,Juliane Adelmann,Matthias Ebbinghaus,E Günther,Marcus Gutmann,Lukas Hahn,Robert Hurwitz,Ralf Krähmer,Frauke Leenders,Tessa Lühmann,Julia Schueler,Luísa Schmidt,Michael Teifel,Lorenz Meinel,Thomas Rudel
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2024-05-09
标识
DOI:10.1021/acsbiomaterials.4c00473
摘要
In recent years, a novel treatment method for cancer has emerged, which is based on the starvation of tumors of amino acids like arginine. The deprivation of arginine in serum is based on enzymatic degradation and can be realized by arginine deaminases like the l-amino acid oxidase found in the ink toxin of the sea hare Aplysia punctata. Previously isolated from the ink, the l-amino acid oxidase was described to oxidate the essential amino acids l-lysine and l-arginine to their corresponding deaminated alpha-keto acids. Here, we present the recombinant production and functionalization of the amino acid oxidase Aplysia punctata ink toxin (APIT). PEGylated APIT (APIT–PEG) increased the blood circulation time. APIT–PEG treatment of patient-derived xenografted mice shows a significant dose-dependent reduction of tumor growth over time mediated by amino acid starvation of the tumor. Treatment of mice with APIT–PEG, which led to deprivation of arginine, was well tolerated.
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