NBMPR-BINDING SITE OF THE HUMAN ES ADENOSINE TRANSPORTER

描述 (摘自申请者的摘要)这是一个被指导的少数族裔学院 发展奖提案旨在提供必要的指导和 为使私家侦探实现其职业目标所必需的研究活动 成为一名公认的独立学术调查员 心血管研究和药物研发领域。该提案回应了 国家心肺血液研究所及时主动提出 让未被充分代表的少数族裔科学家成为独立调查人员。 心血管疾病是美国人的主要死因。 人口，150万美国人患有新的或复发的心脏 袭击，每年造成超过98万人死亡。尤其是少数族裔 非洲裔美国人受到的影响不成比例。绝对有必要 心血管领域更多的少数民族研究人员，特别是在 密西西比州，居住着大量的非裔美国人。这项建议 寻求为私人助理提供密集的指导和研究培训 在一所以白人为主的高等学府担任少数族裔助理教授 密西西比大学。候选人的总体职业目标是 获得蛋白质实验分析领域的研究能力- 利用光标记在分子水平上的配位络合物相互作用， 亲和纯化并用它们在结构上表征 抑制物与ES腺苷(核苷)转运体的相互作用 获得将用于设计和开发更具体和 有效的腺苷转运抑制剂作为潜在的心脏保护和 神经保护性药物。腺苷是一种生理核苷，它是 在缺血状态下释放，如心脏病发作或中风，以保护 组织损伤。然而，核苷转运体对它的快速摄取 这一保护行动。核苷转运抑制剂阻断腺苷 它可以被细胞摄取，从而增强其细胞外保护作用。 抑制腺苷转运在心脏中具有治疗潜力 他设计和发现了尚未开发的疾病和中风 具有必要药理特征的抑制剂。设计的化合物 将作为ES转运体配体和腺苷进行合成和测试 用流式细胞术和放射性同位素方法检测转运抑制剂。这个 应聘者将接受成功人士的指导 调查人员、主要和次要赞助商以及四名高级干部 在候选人咨询委员会任职的教师。辅助课程作业 在先进的蛋白质技术、质谱学和实验设计中， 以及美国化学学会技术研讨会，以及我们的研究 办公车间。两周一次的研究进展会议将与 赞助商和委员会成员。

DESCRIPTION (Adapted from applicant's abstract) This is a Mentored Minority Faculty Development Award Proposal designed to provide the necessary mentoring and research activities necessary to enable the PI achieve his career goals of becoming an established independent academic investigator in the cardiovascular research and drug discovery field. The proposal responds to the timely initiative of the National Heart Lung and Blood Institute to prepare underrepresented minorities scientists as independent investigators. Cardiovascular disease is the number cause of death among the American population, afflicting 1.5 million Americans with a new or recurrent heart attack, and killing over 980,000 people every year. Minorities especially African-Americans are disproportionately affected. There is definitely a need more minority researchers in the cardiovascular field especially in Mississippi, which houses a large African-American Population. This proposal seeks to provide intensive mentoring and research training for the PI who is a minority assistant professor at a predominantly white higher institution, the University of Mississippi. The overall career goals of the candidate are to acquire research capabilities in areas of experimental analysis of protein- ligand complex interactions at the molecular level using photo labeling, affinity purification and use them to structurally characterize the interaction of inhibitors with the es adenosine (nucleoside) transporter to obtain insights that will be used to design and develop more specific and potent adenosine transport inhibitors as potential cardioprotective and neuroprotective drugs. Adenosine is a physiological nucleoside that is released in ischemic conditions such as a heart attack or stroke to protect tissue injury. However, its rapid uptake by nucleoside transporters abrogates this protective action. Nucleoside transport inhibitors block adenosine uptake by cells, and therefore enhance its extracellular protective effects. The inhibition of adenosine transport has therapeutic potential in heart disease and stroke that has yet to be tapped by he design and discovery of inhibitors with the requisite pharmacological profiles. Designed compounds will be synthesized and tested as es transporter ligands and adenosine transport inhibitors by flow cytometry and radioisotope methods. The candidate will receive mentorship by established well-accomplished investigators, the primary and secondary sponsors, and a cadre of four senior faculty serving on the candidates advisory committee. Ancillary course work in advanced protein techniques, mass spectrometry and experimental design, as well as American Chemical Society techniques workshops, and our research office workshops. Biweekly research progress meetings will be held with sponsors and committee members.