کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1998579 1065816 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria
چکیده انگلیسی

Phenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; second, we used silica sol–gel material as a matrix to demonstrate that a silica matrix can provide protection to entrapped PAL proteins against intestinal proteases, as well as a low pH of 3.5; finally, we demonstrated that PEGylation of AvPAL surface lysines can reduce the inactivation of the enzyme by trypsin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 99, Issue 1, January 2010, Pages 4–9
نویسندگان
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