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CARHOHYDRATE MOIETIES OF GP120

GP120 的碳水化合物部分

基本信息

批准号：
2064926
负责人：
KHUSHI L MATTA
金额：
$ 22.75万
依托单位：
ROSWELL PARK CANCER INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-01 至 1995-07-31
项目状态：
已结题

项目摘要

The envelope glycoprotein gp120 of the human immunodeficiency virus (HIV) is a high glycosylated molecule. It has been suggested that gp120 plays a vital role in viral attachment and the initiation of infection through interaction of CD4 glycoprotein of T-lymphocytes. This program centers at the chemical synthesis of oligosaccharide structures which are being reported as part of the carbohydrate moiety of gp120 and their further use as immunogens. Attention will be focussed on the synthesis of glycosides that possess an aglycon which can serve as a bridge for attachment to high molecular weight substances such as bovine serum albumin. Complex structures containing mannose is one of our major interests in this program. We plan to investigate the use of various derivatives of 4- pentenyl-alpha-D-mannopyranoside as glycosylating agents. The structures of our synthetic compounds will be established by n.m.r. studies and mass spectroscopy. Our synthetic antigens will be further utilized to raise their antibodies. The availability of antigen moiety linked to a solid support (Sepharose) will facilitate purification of the antibodies raised against the corresponding antigens. Specificity of the purified antibodies will be established with a battery of our well-defined carbohydrate structures. Upon purification the antibodies produced to the synthetic obligosaccharides will be tested for their ability to block gp120-CD4 binding and gp120-CD4 mediated cell fusion and for their ability to neutralize virus growth. Our synthetic saccharides linked to BSA will be used to develop saccharide ELISA methodology for the detection of anti- carbohydrate antibodies in the sera of AIDS patients. Thus, in the program we also plan to screen AIDS patients' sera for well-defined oligosaccharide specific antibodies. In another aspect of this program, we will emphasize our studies toward the chemical synthesis of various potential inhibitors of glycosidases, such as glucosidases and mannosidases, involved in the processing and biosynthesis of glycoprotein including gp120. The effect of glycosylation inhibitors on gp120 maturation will be assessed in a variety of transfected cell lines and in virus-infected cells. Our potential inhibitors may prove to be chemotherapeutic agents for AIDS.

人类免疫缺陷病毒（HIV）的包膜糖蛋白gp 120 是高度糖基化的分子。有人认为，GP 120起着重要的作用。在病毒附着和感染的启动中起着重要作用， T淋巴细胞CD 4糖蛋白相互作用。该计划的中心是寡糖结构的化学合成，报道为GP 120的碳水化合物部分的一部分以及它们的进一步用途作为免疫原。注意力将集中在糖苷的合成上它拥有一个糖苷配基，可以作为连接高分子的桥梁，分子量物质如牛血清白蛋白。含有甘露糖的复杂结构是我们对此的主要兴趣之一。程序. 我们计划研究4的各种衍生物的使用- 戊烯基-α-D-吡喃甘露糖苷作为糖基化剂。的结构我们的合成化合物将由N.M.R.研究和质量谱我们的合成抗原将进一步用于提高他们的抗体。与固体连接的抗原部分的可用性支持物（琼脂糖凝胶）将有助于纯化产生的抗体针对相应的抗原。纯化抗体的特异性将由一系列我们定义明确的碳水化合物组成结构. 在纯化后，产生针对合成抗体的抗体。将检测异戊烯苷阻断gp 120-CD 4的能力结合和gp 120-CD 4介导的细胞融合，以及它们的中和病毒生长我们合成的连接到BSA的酶将是用于开发检测抗- 艾滋病患者血清中的糖类抗体。因此，在程序中我们还计划在艾滋病患者的血清中筛选明确的寡糖，特异性抗体在这个计划的另一个方面，我们将强调我们的研究，各种潜在的糖苷酶抑制剂的化学合成，例如葡萄糖苷酶和甘露糖苷酶，参与加工和生物合成糖蛋白包括gp 120。糖基化抑制剂对将在多种转染的细胞系中评估gp 120成熟和病毒感染的细胞中。我们的潜在抑制剂可能会被证明是用于AIDS的化疗剂。