Isotope Assisted Site Specific Molecular Structural Determination of Abeta Peptides

在这个由化学系实验物理化学计划资助的奖项中，来自范德比尔特大学的Polavarapu教授和他的学生将研究Abeta肽的分子结构。水溶性α螺旋结构转化为聚集体，形成全长A β肽[淀粉样肽，A β（1-42）]的β折叠结构，被认为是淀粉样疾病发病的原因。为了理解这个过程，需要知道这个过程的启动源。 具体而言，不清楚这种结构转变是在特定氨基酸位点还是在Abeta肽的某个片段处起始。本提案的目的是使用选定的C-13同位素标记的酰胺C=O基团和手性光谱来推断Abeta肽的位点特异性分子结构信息。 本计画中主要的手征光学光谱方法是新近发展的振动圆二色性光谱法。 还将进行伴随的电子圆二色谱（ECD）光谱研究，以补充从VCD研究中获得的结构信息。振动吸收（VA）光谱（与VCD光谱一起沿着自动测量）将用于获得额外的结构信息。为了实现所述目标，将合成并研究同位素标记的短长度Abeta肽。同时量子化学调查的振动特性也将进行同位素标记的短长度Abeta肽，以帮助解释实验光谱。Polavarapu教授将邀请学生参与研究，并计划到附近的少数民族服务机构田纳西州立大学开展外展活动。这所大学的学生将参加夏季研究活动，并被邀请参加每周一次的手光学光谱学夏季讲座。此外，在夏季，将举行为期一周的关于这一技术的讲习班，目标是来自化学工业和学术实验室的混合观众。

In this award, funded by the Experimental Physical Chemistry Program of the Chemistry Division, Professor Polavarapu and his students from Vanderbilt University will investigate the molecular structure of Abeta peptides. The conversion of water soluble alpha helical structure into aggregate forming beta sheet structure for full length Abeta peptide [amyloid peptide, Abeta(1-42)] is thought to be responsible for the onset of amyloid disease. To understand this process, the source of initiation of this process needs to be known. Specifically, it is not understood if this structural transition is initiated at a particular amino acid site, or at a certain segment in the Abeta peptide. The purpose of this proposal is to deduce site-specific molecular structural information of Abeta peptide with the use of selected C-13 isotope labels for the amide C=O groups and chiroptical spectroscopy. The main chiroptical spectroscopic method in this project is the newly developed vibrational circular dichroism (VCD) spectroscopy. Accompanying electronic circular dichroism (ECD) spectral studies will also be undertaken in order to supplement the structural information obtained from VCD studies. Vibrational absorption (VA) spectra, which are automatically measured along with VCD spectra, will be used to gain additional structural information. To accomplish the stated goals, isotope labeled short length Abeta peptides will be synthesized and investigated. Simultaneous quantum chemical investigations of vibrational properties will also be undertaken for the isotope labeled short length Abeta peptides to aid in the interpretation of experimental spectra. These combined experimental and quantum chemical investigations on isotope labeled short length peptides are hoped to provide site-specific molecular structural information for Abeta peptide.Professor Polavarapu will involve students in research and plans outreach activities to a nearby minority serving institution, Tennessee State University. Students from this university will participate in summer research activities, and are invited to attend weekly summer lectures on chiroptical spectroscopy. Also in the summers, week-long workshops on this technique will be held, targeting a mixed audience from chemical industry and academic laboratories.