International Research Fellowship Program: New Chemical Approaches to Glycopeptide Assembly with Application to the Development of New Antigen Motifs for Vaccine Therapy in HIV

0502139塔利国际研究奖学金计划使美国科学家和工程师能够在国外进行三到二十四个月的研究。该计划的奖项提供了联合研究的机会，以及使用独特或互补的设施，专业知识和国外的实验条件。Tully与Pauline M博士合作。大多数成功的疫苗都是利用中和抗体的力量来激发它们的作用。由于包膜蛋白碳水化合物保护肽骨架免受抗体识别的能力，这种用于人类免疫缺陷病毒1型（HIV-1）的疫苗的开发受到阻碍。最近，发现人抗体2G 12（中和广泛范围的HIV-1分离物的抗体）识别包膜蛋白上的碳水化合物部分簇。与2G 12抗体类似的糖蛋白文库的产生将使得能够开发用于HIV-1疫苗制剂的不同抗体。为了创建这样的文库，PI和她的宿主正在开发一种用于生产N-连接糖蛋白的聚合合成方法。他们的方法将具有广泛的实用性，使得来自化学合成或来自纯化的糖蛋白水解产物的聚糖可以在没有保护基团的情况下连接到水中的合成肽序列上，并建立存在于N-连接的糖蛋白中的正确的b-乙酰氨基酰胺键。然后，他们将探索他们的合成方法的实用性，通过构建一个糖蛋白库，表达两个富含甘露糖的聚糖结构的空间分辨位点作为模型的表位2G 12和作为抗原的抗体产生具有类似的活性。Rudd博士的实验室已经建立了许多国际研究合作与一些最好的实验室在糖生物学。

0502139TullyThe International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-two-month research fellowship by Dr. Sarah E. Tully to work with Dr. Pauline M. Rudd at Oxford University in the United Kingdom.Most successful vaccines utilize the power of neutralizing antibodies to elicit their effects. Development of such a vaccine for human immunodeficiency virus type 1 (HIV-1) has been hampered due to the ability of envelope protein carbohydrates to protect the peptide backbone from antibody recognition. Recently, human antibody 2G12, an antibody that neutralizes a broad range of HIV-1 isolates, was found to recognize a cluster of carbohydrate moieties on the envelope protein. Generation of a library of glycoproteins similar to the 2G12 antibody would enable the development of different antibodies for HIV-1 vaccine formulations. To create such a library, the PI and her host are developing a convergent synthetic approach for the production of N-linked glycoproteins. Their methodology will have broad-based utility such that glycans, derived from chemical synthesis or from purified glycoprotein hydrolysates, can be attached without protecting groups to a synthetic peptide sequence in water with establishment of the correct b-aspartyl amide linkage present in N-linked glycoproteins. They will then explore the utility of their synthetic approach by constructing a glycoprotein library expressing two mannose-rich glycan structures in spatially-resolved loci as a model for the epitope of 2G12 and as an antigen for the generation of anibodies with similar activity.Dr. Rudd's laboratory has established numerous international research collaborations with some of the best laboratories in glycobiology.