کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1362368 981486 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhancement of oral drug absorption—Effect of lipid conjugation on the enzymatic stability and intestinal permeability of l-Glu-l-Trp-NH2
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Enhancement of oral drug absorption—Effect of lipid conjugation on the enzymatic stability and intestinal permeability of l-Glu-l-Trp-NH2
چکیده انگلیسی

The dipeptide l-Glu-l-Trp-OH (IM862) is currently under development for the treatment of certain cancers and immuno-deficiency disorders. However, due to its highly hydrophilic character, IM862 demonstrates low permeability across biological membranes, including the gastro-intestinal track, which makes it not orally available. In this study, the effect of lipid conjugation on the stability and intestinal permeability of the IM862 amide derivative l-Glu-l-Trp-NH2 was investigated using enzymatic extracts and monolayers of Caco-2 cells, respectively. A series of eleven novel lipopeptide analogues of l-Glu-l-Trp-NH2 was synthesized using tert-butyloxycarbonyl or 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis. In vitro assays demonstrated an improved stability to proteolytic enzymes and increased intestinal permeability for several conjugates, thereby supporting the hypothesis that lipidation may provide a means to enable the oral administration of IM862.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 22, 15 November 2007, Pages 7048–7057
نویسندگان
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