کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1377839 981989 2006 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of downsized metastin (45–54) analogs with maintenance of high GPR54 agonistic activity
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of downsized metastin (45–54) analogs with maintenance of high GPR54 agonistic activity
چکیده انگلیسی

Metastin has been identified as a metastasis suppressor gene product that mediates its function through a G protein coupled receptor, GPR54. To refine insight into the critical pharmacophore for the activation of GPR54, we have conducted alanine and d-amino acid scanning on a biologically active metastin fragment (45–54). Based on these data and structures of peptides previously reported to activate GPR54, a series of shortened metastin (45–54) derivatives were synthesized and tested for the ability to induce GPR54 signaling. These biological experiments were performed in yeast containing human GPR54 that was coupled to the pheromone response pathway and a pheromone responsive lacZ reporter gene. Compounds 32, 33, and 39, which possess an N-terminal basic group and a C-terminal RW-amide motif, were strong agonists, similar to the level of metastin. This may provide an approach to reverse the pro-metastatic effect of metastin deletion in multiple malignant tumors.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 1, 1 January 2006, Pages 134–137
نویسندگان
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