Synthesis and Study of Novel Sensing Agents

描述（由申请人提供）：该更新申请是通过设计具有高分析物特异性的合成有机指示剂来检测可见光谱区域中无色生物分子的努力的延续。该计划的广泛，长期目标是通过创建实用的生物医学研究新工具来促进疾病的诊断和理解。血浆同型半胱氨酸（Hcy）水平升高与心肌梗死、中风和静脉血栓栓塞的风险增加相关。同型半胱氨酸还与阿尔茨海默病、神经管缺陷和妊娠期并发症、炎症性肠病和骨质疏松症的风险增加有关。尽管经过20多年的深入研究，同型半胱氨酸在疾病中的实际作用仍然不清楚。目的是有助于（i）澄清目前对同型半胱氨酸在疾病中的作用的理解和（ii）促进天然介质中同型半胱氨酸的研究。解决这两个问题的方法植根于基础有机化学。揭示Hcy与其他硫醇和生物分子之间的基本有机化学差异将提供与Hcy参与疾病相关的新知识，并同时导致高度选择性和使新的检测方法成为可能。为了实现这些目标，提出了以下具体目标：目标1。高选择性指示剂，用于简化同型半胱氨酸的测定。目标二。同型半胱氨酸衍生的α-氨基碳中心自由基化学的新见解。目标3：蛋白质结合同型半胱氨酸的检测和化学。该项目的每个具体目标都涉及提高同型半胱氨酸的检测。在人类中存在高于一定水平的同型半胱氨酸通常表明严重的疾病风险。这种有用的氨基酸生物标志物已经研究了几十年，但它在疾病中的作用仍然不清楚。我们建议创建更简单的新方法和材料检测同型半胱氨酸，以及澄清其在疾病中的作用。

DESCRIPTION (provided by applicant): This renewal application is a continuation of efforts to detect colorless biomolecules in the visible spectral region by designing synthetic organic indicators with high analyte specificity. The broad, long-term objective of this program is to facilitate the diagnosis and understanding of disease via the creation of practical new tools for biomedical research. Elevated plasma homocysteine (Hcy) levels are associated with increased risk of myocardial infarction, stroke and venous thromboembolism. Homocysteine has also been linked to increased risk of Alzheimer's disease, neural tube defects and complications during pregnancy, inflammatory bowel disease and osteoporosis. Despite over 20 years of intense study, the actual role of homocysteine in disease remains unclear. The goals are to contribute to (i) clarifying the current understanding of the role of homocysteine in disease and (ii) facilitate the study homocysteine in natural media. The approach to these two issues is rooted in fundamental organic chemistry. Uncovering the differences in the basic organic chemistry between Hcy and other thiols and biomolecules will afford new knowledge relevant to Hcy's involvement in disease and concurrently lead to highly selective and enabling new detection methods. To approach these goals, the following Specific Aims are proposed: Aim 1. Highly selective indicators for simplifying the determination of homocysteine. Aim 2. New insights into the chemistry of the homocysteine-derived alpha-amino carbon-centered radical. Aim 3. Detection and chemistry of protein-bound homocystamide. Each of the Specific Aims of this project involves improving the detection of homocysteine. The presence of homocysteine above certain levels in humans often indicates serious risk for disease. This useful amino acid biomarker has been studied for decades, but its role in disease is still not clear. We propose to create simpler new methods and materials for homocysteine detection as well as clarification of its role in disease.