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• W2078605112 abstract "Peptide oral delivery is still a significant challenge because of two major impediments, low absorption efficiency and instability in gastrointestinal tract. The aim of this study was to design, prepare, and evaluate an intestine enzyme-resistant, superior intestine absorptive, and biologically preserved glucagon-like peptide-1 (GLP-1) derivative using the site-specific modification of biotin, which can take advantage of the carrier-mediated active intestine transport. Two series of site-specific Lys34- and Lys26,34–biotin–GLP-1 derivatives were prepared, and their intestine membrane permeabilities, proteolytic stabilities against the intestine enzymes, and bioactivities were then evaluated. Especially, Lys26,34–biotin–GLP-1 was found to have the most promising scores: (i) it displayed a 5.6-fold higher Caco-2 cell monolayer permeability than GLP-1; (ii) it showed an 8.5- and 3.5-fold longer half-life than GLP-1 in rat intestine fluid and homogenate, respectively; and interestingly (iii) it had a well-preserved insulinotropic activity (94.5% vs. GLP-1) in the rat islets. Finally, Lys26,34–biotin–GLP-1 showed a 9-fold higher oral hypoglycemic efficacy (25.3%) than native GLP-1 (2.7%) (P < 0.005) after direct peroral administration into type 2 diabetic db/db mice. This study highlights the oral hypoglycemic potential of site-specific Lys26,34-biotinylated GLP-1, and this orally available analogue would find a role in the treatment of type 2 diabetes." @default.
• W2078605112 created "2016-06-24" @default.
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• W2078605112 date "2008-03-01" @default.
• W2078605112 modified "2023-09-27" @default.
• W2078605112 title "Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: Design, preparation, and biological evaluation" @default.
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• W2078605112 doi "https://doi.org/10.1016/j.ejpb.2007.07.009" @default.
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