Isotope Assisted Site Specific Molecular Structural Determination of Abeta Peptides

在这个由化学系实验物理化学项目资助的奖项中，来自范德比尔特大学的Polavarapu教授和他的学生将研究Abeta多肽的分子结构。水溶性α螺旋结构转化为聚集体形成全长Abeta多肽[Aβ(1-42)]的β片状结构被认为是淀粉样病的发病原因。要理解这一进程，需要知道这一进程的启动来源。具体地说，目前还不清楚这种结构转变是在特定的氨基酸位点启动的，还是在Abeta肽的特定片段启动的。这一建议的目的是利用选定的酰胺C=O基团的C-13同位素标记和手性光谱来推断Aβ多肽的特定部位的分子结构信息。本项目中的主要手性光谱方法是新开发的振动圆二色谱(VCD)光谱。同时还将进行电子圆二向色性(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光谱一起被自动测量，将用于获得额外的结构信息。为了实现上述目标，将合成和研究同位素标记的短长度Aβ多肽。同时还将对同位素标记的短长度Abeta多肽进行振动性质的量子化学研究，以帮助解释实验光谱。这些对同位素标记的短肽的联合实验和量子化学研究有望为Abeta肽提供特定位置的分子结构信息。Polavarapu教授将让学生参与研究，并计划到附近的少数族裔服务机构田纳西州立大学开展外联活动。这所大学的学生将参加暑期研究活动，并被邀请参加每周一次的手部光谱学暑期讲座。同样在夏季，还将举办为期一周的关于这项技术的研讨会，目标是来自化学工业和学术实验室的混合受众。

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.