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Sulfated glycopeptide nanostructures for multipotent protein activation
Nature Nanotechnology ( IF 38.3 ) Pub Date : 2017-06-19 00:00:00 , DOI: 10.1038/nnano.2017.109
Sungsoo S. Lee , Timmy Fyrner , Feng Chen , Zaida Álvarez , Eduard Sleep , Danielle S. Chun , Joseph A. Weiner , Ralph W. Cook , Ryan D. Freshman , Michael S. Schallmo , Karina M. Katchko , Andrew D. Schneider , Justin T. Smith , Chawon Yun , Gurmit Singh , Sohaib Z. Hashmi , Mark T. McClendon , Zhilin Yu , Stuart R. Stock , Wellington K. Hsu , Erin L. Hsu , Samuel I. Stupp

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

中文翻译:

硫酸糖肽纳米结构,用于多能蛋白质活化

为了优化其功能,生物系统已经进化为利用众多具有结合多糖能力的蛋白质。具有高度多样化的硫酸化多糖的结合域的这些蛋白质的众所周知的子集是参与生物发育和组织修复的重要生长因子。我们在这里报告超分子硫酸化的糖肽纳米结构,其表面上显示三硫酸化的单糖,并结合具有不同多糖结合域的五个关键蛋白。结合不会破坏纳米结构的丝状形状或它们内部的β-sheet骨架,但必须包含可访问的适应性构型以与这种不同的蛋白质相互作用。糖肽纳米结构比天然硫酸化多糖肝素显着地增强了骨形态发生蛋白2的信号传导,并以比动物模型中所需剂量低100倍的蛋白质剂量促进了脊柱中骨骼的再生。这些具有高度生物活性的纳米结构可能在将来使涉及蛋白质的许多疗法成为可能。
更新日期:2017-06-20
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