کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1377533 981981 2007 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tetrapeptide inhibitors of the glutamate vesicular transporter (VGLUT)
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Tetrapeptide inhibitors of the glutamate vesicular transporter (VGLUT)
چکیده انگلیسی

Quinoline-2,4-dicarboxylic acids (QDCs) bearing lipophilic substituents in the 6- or 7-position were shown to be inhibitors of the glutamate vesicular transporter (VGLUT). Using the arrangement of the QDC lipophilic substituents as a template, libraries of X1X2EF and X1X2EW tetrapeptides were synthesized and tested as VGLUT inhibitors. The peptides QIEW and WNEF were found to be the most potent. Further stereochemical deconvolution of these two peptides showed dQlIdElW to be the best inhibitor (Ki = 828 ± 252 μM). Modeling and overlay of the tetrapeptide inhibitors with the existing pharmacophore showed that H-bonding and lipophilic residues are important for VGLUT binding.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 18, 15 September 2007, Pages 5125–5128
نویسندگان
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