کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2007259 1066368 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of a novel dual E- and N-cadherin antagonist
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Identification of a novel dual E- and N-cadherin antagonist
چکیده انگلیسی

E- and N-cadherin are related calcium-dependent cell adhesion molecules that exert an influence over multiple biological and disease processes. Antagonists of these cadherins can therefore be envisaged as therapeutically useful drugs. We have used phage display technology to discover such antagonists. A peptide phage library was screened against a chimeric protein composed of the human E-cadherin ectodomain fused to the Fc fragment of human immunoglobulin G1 (E-cad/Fc). All of the phage clones that were isolated also bound a chimeric protein composed of the human N-cadherin ectodomain fused to the Fc fragment of human immunoglobulin G1 (N-cad/Fc). A peptide displayed by several of the isolated phage clones was synthesized (H-SWELYYPLRANL-NH2) and found to bind both E- and N-cad/Fc chimeric proteins with affinities (KD) of 9.4 μM and 323 nM, respectively, as judged by surface plasmon resonance spectroscopy. This peptide was also capable of blocking the aggregation of E- and N-cad/Fc chimeric protein-coated beads, as well as the aggregation of MCF-7 and MDA-MB435 human breast cancer cells (these cells express E- and N-cadherin, respectively). Finally, we showed that the peptide disrupted MCF-7 and MDA-MB435 cell monolayers. The peptide, H-SWELYYPLRANL-NH2 thus proved to be a biologically active, dual E- and N-cadherin antagonist. Such an antagonist has application in a wide variety of biological contexts.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 30, Issue 8, August 2009, Pages 1539–1547
نویسندگان
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