SYNTHESIS, ANALYSIS, TOXICITY SCREENING AND COMPUTATIONAL CHEMISTRY OF ARYLPHOSP

芳基膦的合成、分析、毒性筛选和计算化学

• 批准号: 7609981
• 负责人: John Charles Williams
• 金额: $ 2.17万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609981
• 关键词: Anti-Bacterial Agents; Bacteria; Binding; Biological Availability; Biology; Cations; Chemistry; Chromatography; Computer Analysis; Computer Retrieval of Information on Scientific Projects Database; DNA; Docking; Education; Faculty; Funding; Grant; High Pressure Liquid Chromatography; Individual; Industry; Institution; Ions; Laboratory Research; Learning; Lipids; Medicine; Mentors; Methods; Microbiology; Mitochondria; Organic Chemistry; Pharmacology; Phase; Positioning Attribute; Quantitative Structure-Activity Relationship; Research; Research Personnel; Research Project Grants; Resources; Sampling; Screening procedure; Source; Structure; Students; Techniques; Toxic effect; Training Support; United States National Institutes of Health; Work; cancer cell; career; computational chemistry; cytotoxic; experience; killings; melting; molecular dynamics; molecular mechanics; polypeptide

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Synthesis and characterization, toxicity screening, chromatography, and computational analysis of arylphosphonium cations conjugated with lipids or polypeptides will be done by undergraduate chemistry and biology students in which they will use experimental bench, instrumental, and computational chemistry methods learned in organic chemistry and microbiology and apply and refine them in application to a research project. The compound type is generally cytotoxic. It accumulates in mitochondria of malignant cells, binds to acetylcholineserase, shifts the melting curve of native DNA, kills a variety of gram-postive bacteria, and malignant cells in culture. QSAR, molecular mechanics, and molecular dynamics calculations will be done, repectively; to find correlations with and predictors of activity (QSAR), to determine DNA/Binder docking geometries and energies (mm), and to observe thermal degradation of dsDNA with and without a binder present (md). Reversed-phase HPLC and TLC using ion-pair techniques will be used to determine chromatographic constants that are physical correlates of bioavailability. Microscale synthesis, purification and analysis of compounds at the 50-100 mg scale will help students develop accuracy and precision in experimental technique. They will routinely prepare samples and acquire and analyze IR, NMR, UV and (in some cases) fluoresence spectra. LC-MS will be used in lieu of elemental analysis as verification of structure for new compounds. One or more will do Kirby-Bauer antibacterial screening. The students will earn money to support their education while gaining experience in laboratory research under the direction of faculty mentors. This will provide support and training for individuals who intend to pursue graduate work in chemistry, biology, medicine, or pharmacology, as well as help prepare them for entry-level (BA and BS) positions in chemistry, biology or health-related positions in industry. The high-profile presence of these students doing this work in our departments will help attract others to consider careers in research.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 合成和表征，毒性筛选，色谱法和计算分析芳基磷鎓阳离子与脂质或多肽共轭将由本科化学和生物学学生完成，他们将使用实验台，仪器和计算化学方法在有机化学和微生物学中学习，并将其应用于研究项目。化合物类型通常具有细胞毒性。它在恶性细胞的线粒体中积累，与乙酰胆碱酯酶结合，改变天然DNA的熔解曲线，杀死各种革兰氏阳性菌和培养中的恶性细胞。将分别进行QSAR、分子力学和分子动力学计算;以发现与活性的相关性和活性的预测因子（QSAR），以确定DNA/结合剂对接几何形状和能量（mm），并观察存在和不存在结合剂的dsDNA的热降解（md）。采用离子对技术的反相HPLC和TLC将用于测定作为生物利用度物理相关性的色谱常数。在50-100毫克规模的化合物的微型合成，纯化和分析将帮助学生发展实验技术的准确性和精密度。他们将常规制备样品，并获取和分析IR，NMR，UV和（在某些情况下）荧光光谱。 将使用LC-MS代替元素分析验证新化合物的结构。一个或多个人将做Kirby-Bauer抗菌筛选。学生将赚钱来支持他们的教育，同时在教师导师的指导下获得实验室研究的经验。这将为打算从事化学，生物学，医学或药理学研究生工作的个人提供支持和培训，并帮助他们为化学，生物学或健康相关职位的入门级（BA和BS）职位做好准备。这些学生在我们部门做这项工作的高调存在将有助于吸引其他人考虑研究职业。