کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5433504 | 1508990 | 2017 | 14 صفحه PDF | دانلود رایگان |
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly2]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic. Here, we designed and prepared a new degradation-resistant GLP-2 analogue dimer, designated GLP-2â¡, with biotechnological techniques. The purity of GLP-2â¡reached 97% after ammonium sulphate precipitation and anion exchange chromatography purification, and the purification process was simple and cost-effective. We next confirmed that the GLP-2â¡ exhibited enhanced activities compared with [Gly2]GLP-2, the long-acting, degradation-resistant analogue. Notably, GLP-2â¡ offers a pharmacokinetic and therapeutic advantage in the treatment of radiation-induced intestinal injury over [Gly2]GLP-2. We further demonstrated that GLP-2â¡ rapidly activates divergent intracellular signaling pathways involved in cell survival and apoptosis. Taken together, our data revealed a potential novel and safe peptide drug for limiting the adverse effect of radiotherapy on the gastrointestinal system.
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Journal: Journal of Controlled Release - Volume 260, 28 August 2017, Pages 32-45