†Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
‡Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424 Potsdam, Germany.
Biomacromolecules. 2015 Jul 13;16(7):2188-97. doi: 10.1021/acs.biomac.5b00572. Epub 2015 Jun 4.
Self-assembling peptides can be used to create tunable higher-order structures for the multivalent presentation of a variety of ligands. We describe a novel, fiber-forming coiled-coil-based peptide that assembles to display, simultaneously, carbohydrate and peptide ligands recognized by biomacromolecules. Preassembly decoration of the scaffold with a diphtheria toxin peptide epitope or a mannose motif did not interfere with self-assembly of the nanostructure. The resulting multivalent display led to tighter binding by antidiphtheria toxin antibodies and mannose-specific carbohydrate binding proteins, respectively. The potential of this self-assembling peptide to display ligands in bioanalytical assays is illustrated by its decoration with a disaccharide glycotope from the Leishmania parasite. Carbohydrate-specific antibodies produced in response to a Leishmania infection are detected more sensitively in human and canine sera due to the multivalent presentation on the self-assembled scaffold. Thus, nanofibers based on coiled-coil peptides are a powerful tool for the development of bioassays and diagnostics.
自组装肽可用于构建可调谐的高阶结构，以实现多种配体的多价呈现。我们描述了一种新型的、基于纤维形成的卷曲螺旋肽，它能够同时展示糖肽和肽配体，这些配体被生物大分子识别。支架的预组装用白喉毒素肽表位或甘露糖基序进行修饰，不会干扰纳米结构的自组装。由此产生的多价展示分别导致抗白喉毒素抗体和甘露糖特异性碳水化合物结合蛋白的结合更紧密。通过将二糖糖基从利什曼原虫寄生虫上的糖基化肽修饰到自组装支架上，说明了这种自组装肽在生物分析测定中展示配体的潜力。由于自组装支架上的多价呈现，针对利什曼原虫感染产生的碳水化合物特异性抗体在人血清和犬血清中的检测更灵敏。因此，基于卷曲螺旋肽的纳米纤维是开发生物测定和诊断的有力工具。
