Institut de Biotecnologia i de Biomedicina , Universitat Autònoma de Barcelona , Bellaterra 08193 Barcelona , Spain.
Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales, ICTA and Departamento de Química, Cátedra de Química Biológica, Córdoba, Argentina, CONICET, Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), Córdoba, Argentina , Av. Velez Sarsfield 1611 , X5016GCA Córdoba , Argentina.
Biomacromolecules. 2018 Sep 10;19(9):3788-3797. doi: 10.1021/acs.biomac.8b00924. Epub 2018 Aug 13.
Protein materials are rapidly gaining interest in materials sciences and nanomedicine because of their intrinsic biocompatibility and full biodegradability. The controlled construction of supramolecular entities relies on the controlled oligomerization of individual polypeptides, achievable through different strategies. Because of the potential toxicity of amyloids, those based on alternative molecular organizations are particularly appealing, but the structural bases on nonamylogenic oligomerization remain poorly studied. We have applied spectrofluorimetry and spectropolarimetry to identify the conformational conversion during the oligomerization of His-tagged cationic stretches into regular nanoparticles ranging around 11 nm, useful for tumor-targeted drug delivery. We demonstrate that the novel conformation acquired by the proteins, as building blocks of these supramolecular assemblies, shows different extents of compactness and results in a beta structure enrichment that enhances their structural stability. The conformational profiling presented here offers clear clues for understanding and tailoring the process of nanoparticle formation through the use of cationic and histidine rich stretches in the context of protein materials usable in advanced nanomedical strategies.
蛋白质材料由于其内在的生物相容性和完全可生物降解性，在材料科学和纳米医学领域迅速引起关注。超分子实体的可控构建依赖于通过不同策略实现的单个多肽的可控寡聚化。由于淀粉样蛋白的潜在毒性，基于替代分子组织的那些特别吸引人，但非淀粉样蛋白寡聚化的结构基础仍研究甚少。我们已经应用荧光光谱法和旋光光谱法来鉴定 His 标记的阳离子伸展物在形成直径约为 11nm 的规则纳米颗粒过程中的构象转换，这些纳米颗粒可用于肿瘤靶向药物传递。我们证明了作为这些超分子组装构建块的蛋白质获得的新构象具有不同程度的紧凑性，并导致β结构的富集，从而增强了它们的结构稳定性。这里呈现的构象分析为理解和定制纳米颗粒形成过程提供了明确的线索，该过程通过在可用于先进纳米医学策略的蛋白质材料中使用阳离子和富含组氨酸的伸展来实现。
