کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362368 | 981486 | 2007 | 10 صفحه PDF | دانلود رایگان |

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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Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 22, 15 November 2007, Pages 7048–7057