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首页> 外文学位 >Unfolded, misfolded, and self-organized short alanine-rich peptides: Implications for fundamental science, human disease, and biotechnology.
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Unfolded, misfolded, and self-organized short alanine-rich peptides: Implications for fundamental science, human disease, and biotechnology.

机译：折叠，折叠和自组织的富含丙氨酸的短肽：对基础科学，人类疾病和生物技术的意义。

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摘要

Protein folding is the reversible transition by which an unordered polypeptide chain attains its functional 3-D native structure. A detailed understanding of the principles which govern the protein folding process, such as how sequence codes for structure, remains elusive. Achieving a complete picture of the folding process requires information regarding structural preferences in the unfolded state. Moreover, understanding the principles which govern protein aggregation is of significant biomedical and biotechnological importance. Herein, short alanine-based peptides are used as model systems for studying both the structural preferences in the unfolded state as well as protein aggregation in relation to human disease, and exploitation of the self-assembly process for various biotechnological applications.It is now a central dogma of protein science that the unfolded state is not conformationally random, as was originally believed, but that, instead, residual structure exists. Here, we elucidate the conformational propensities of alanine in the unfolded state using short alanine-rich peptides as model systems. The intrinsic conformational propensities of alanine, as well as nearest neighbor effects are illuminated using various vibrational spectroscopic methods, combined with NMR results.Protein and peptide aggregation is affiliated with various seemingly unrelated diseases, including several neurodegenerative diseases and the systemic amyloidoses. It is of current belief that aggregation is a general feature of the protein energy landscape, suggesting that the various unrelated human pathologies linked to protein aggregation are linked by common principles. Herein, fibril formation of a short alanine-based peptide with no known disease affiliation is probed by vibrational circular dichroism (VCD) spectroscopy. In particular, it is demonstrated that peptide fibrils give rise to VCD intensity enhancement, illustrating the use of the technique as a novel means to probe aggregation kinetics.In addition to the biomedical relevance, protein and peptide self-assembly can be exploited as a means of constructing biomaterials with inherent biofunctionality. In this regard, oligopeptide-based hydrogels have shown potential as drug delivery systems and tissue engineering scaffolds. Herein, the unique properties of a novel class of self-assembling alanine-rich oligopeptides are presented. In particular, it is demonstrated that conformational instability can be exploited to tune the physicochemical properties of hydrogels formed by such systems, for the potential use in various biotechnological applications.
机译：蛋白质折叠是可逆转变，无序多肽链可通过该转变获得其功能性3-D天然结构。对控制蛋白质折叠过程的原理（例如序列的结构编码方式）的详细了解仍然难以捉摸。要获得折叠过程的完整图片，需要有关展开状态下的结构偏好的信息。此外，了解控制蛋白质聚集的原理具有重要的生物医学和生物技术重要性。本文中，基于丙氨酸的短肽被用作模型系统，以研究与人类疾病相关的未折叠状态下的结构偏好以及蛋白质聚集，以及针对各种生物技术应用的自组装过程。蛋白质科学的中心教条认为，展开状态并非如最初所认为的那样是构象随机的，而是存在残留结构。在这里，我们使用短的富含丙氨酸的肽作为模型系统阐明了处于折叠状态的丙氨酸的构象倾向。丙氨酸的内在构象倾向以及最邻近效应通过各种振动光谱方法结合NMR结果进行了阐明。蛋白质和肽的聚集与多种看似无关的疾病有关，包括几种神经退行性疾病和全身性淀粉样蛋白。目前认为，聚集是蛋白质能量格局的普遍特征，这表明与蛋白质聚集相关的各种不相关的人类病理是通过共同的原理联系在一起的。在此，通过振动圆二色性（VCD）光谱探测了没有已知疾病隶属关系的短的基于丙氨酸的肽的原纤维形成。尤其是，已证明肽原纤维会增强VCD的强度，说明该技术已被用作探测聚集动力学的新手段。除生物医学相关性外，还可以利用蛋白质和肽自组装作为手段具有固有生物功能的生物材料的制造。在这方面，基于寡肽的水凝胶已显示出作为药物递送系统和组织工程支架的潜力。在此，提出了新颖的一类自组装的富含丙氨酸的寡肽的独特性质。特别地，证明了可以利用构象不稳定性来调节由这种系统形成的水凝胶的物理化学性质，以潜在地用于各种生物技术应用中。

著录项

  • 作者

    Measey, Thomas J.;

  • 作者单位

    Drexel University.;

  • 授予单位 Drexel University.;
  • 学科 Chemistry Physical.Biophysics General.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 205 p.
  • 总页数 205
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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