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Special Issue: Human and murine redox protein atlases

机译:特刊:人和鼠氧化还原蛋白图谱

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AdnectinsTM are a new family of therapeutic proteins based on the 10th fibronectin type III domain, and designed to bind with high affinity and specificity to therapeutically relevant targets. Adnectins share with antibody variable domains a beta-sheet sandwich fold with diversified loops, but differ from antibodies in primary sequence and have a simpler, single-domain structure without disulfide bonds. As a consequence, Adnectins bind targets with affinity and specificity as high as those of antibodies, but are easier to manipulate genetically and compatible with bacterial expression systems. Adnectins that bind macromolecular targets with nanomolar and picomolar affinity have been selected using in vitro evolution methods, including mRNA display, phage display and yeast display. CT-322, a PEGylated, anti-angiogenic Adnectin that binds vascular endothelial growth factor (VEGF) receptor 2 and blocks its interaction with VEGF A, C and D, is being evaluated in Phase II clinical trials for efficacy in several oncology indications. The Author 2010. Published by Oxford University Press.2010This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited
机译:AdnectinsTM是基于第十个纤连蛋白III型结构域的新型治疗蛋白家族,旨在与治疗相关靶标高亲和力和特异性结合。 Adnectins与抗体可变域共享具有多样化环的β-折叠三明治折叠,但与抗体的一级序列不同,并且具有更简单的单域结构,没有二硫键。结果,Adnectin以与抗体一样高的亲和力和特异性结合靶标,但更易于遗传操作并与细菌表达系统兼容。使用体外进化方法,包括mRNA展示,噬菌体展示和酵母展示,已经选择了具有纳摩尔和皮摩尔亲和力的结合大分子靶标的阿连菌素。 II期临床试验正在评估CT-322,一种结合了血管内皮生长因子(VEGF)受体2并阻断其与VEGF A,C和D相互作用的PEG化抗血管生成Adnectin,其在多种肿瘤适应症中的功效正在评估中。作者2010年。由牛津大学出版社出版。2010年这是一个开放获取文章,根据知识共享署名非商业许可(http://creativecommons.org/licenses/by-nc/2.5)的条款分发,允许无限制使用在适当引用原始作品的前提下,在任何媒体上进行非商业性使用,发行和复制

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