Cell-Surface Glycoconjugates III

在化学学部有机与大分子化学项目的支持下，亚利桑那大学化学系的Robin Polt教授将专注于糖肽合成的特定化学目标和生物物理特性，这些糖肽被设计成以类似于人类大脑中通常发现的内源性激素的方式与膜相互作用。糖基化和非糖基化的两性α螺旋的研究将通过化学合成fmoc保护的o -连接糖基氨基酸来促进，这些氨基酸可以被纳入螺旋肽序列。通过改变螺旋的亲疏水表面积的相对数量和空间分布，可以产生具有不同双层亲和度的糖肽，并通过多种生物物理方法对其进行研究。用于构象分析的经典溶液H(1)-NMR蛋白质方法可以在氘化胶束和双束存在的情况下利用，模拟双层环境。分子力学（蒙特卡罗方法）将由核Overhauser （NOE）数据指导，以了解糖肽在环境从水（均质介质）变为两亲（非均质介质）时的构象组合。固态H(2)-NMR和N(15)-NMR方法将用于观察糖肽螺旋在定向脂质双分子层中的取向，并观察其对双分子层结构的影响。根据观察到的结构，将计算亲水和疏水表面积。在化学学部有机动力学项目的支持下，Polt教授将研究糖肽与膜双层的相互作用，这方面的研究尚未得到很好的研究，但可能会影响对多种生物现象的理解，如肽/糖肽激素和神经递质与受体的相互作用、肽抗原的显示和病毒进入机制。拟议活动产生的更广泛影响包括培养来自不同文化和种族背景的研究生、本科生和研究生研究人员。目前，波尔特集团代表了一个国际化和多元文化的环境，由来自韩国、肯尼亚、爱尔兰、墨西哥和中国以及美国的男女研究生、本科生和研究生组成。学生参与研究的各个方面，包括实验室工作，论文和提案的写作和展示，参加国际科学会议和会议，以及本科生和其他研究生的培训。学生的研究工作获得了NSF（奖学金）、Goldwater基金会、Galileo Circle、McNair奖学金和ARCS基金会颁发的院系、大学和国家级奖项。

With the support of the Organic AND Macromolecular Chemistry Program in the Chemistry Division, Professor Robin Polt, of the Chemistry Department at the University of Arizona, will focus on specific chemical goals of synthesis and biophysical characterization of glycopeptides that are designed to interact with membranes in ways similar to that of endogenous hormones normally found in the human brain. Studies of glycosylated and unglycosylated amphipathic alpha helices will be facilitated by the chemical synthesis of Fmoc-protected O-linked glycosyl-amino acids that can be incorporated into helical peptide sequences. By varying the relative amount and spatial distribution of the hydrophilic and hydrophobic surface areas of the helices, glycopeptides with different bilayer affinities can be created and studied by several biophysical methods. Classical solution H(1)-NMR protein methods for conformational analysis can be exploited in the presence of deuterated micelles and bicelles that mimic bilayer environments. Molecular mechanics (Monte Carlo methods) will be directed by nuclear Overhauser (NOE) data to understand the conformational ensembles of the glycopeptides as the environment is changed from aqueous (homogeneous media) to amphipathic (heterogeneous media). Solid-state H(2)-NMR and N(15)-NMR methods will be used to observe the orientation of glycopeptides helices with respect to oriented lipid bilayers, as well as to observe their effect on bilayer structure. Based on the observed structures, hydrophilic and hydrophobic surface areas will be calculated.With the support of the Organic Dynamics Program in the Chemistry Division, Professor Polt will examine interaction of glycopeptides with membrane bilayers, which is not well studied, but is likely to impact the understanding of such diverse biological phenomena as the interaction of peptide/glycopeptide hormones and neurotransmitters with receptors, display of peptide antigens, and mechanisms of viral entry. Broader Impacts resulting from the proposed activity include the training of graduate, undergraduate and post-graduate researchers from diverse cultural and ethnic backgrounds. Presently, the Polt Group represents an international and multicultural environment, consisting of male and female graduate, undergraduate, and post-graduate students from Korea, Kenya, Ireland, Mexico and China, as well as from the United States. Students participate in every aspect of research, including the laboratory work, writing and presentation of papers and proposals, participating in international scientific meetings and conferences, as well as in the training of undergraduates and other graduate students. Students have won awards at the departmental, university and national levels for their research work from NSF (Fellowships), the Goldwater Foundation, Galileo Circle, McNair Fellowship, and the ARCS Foundation.