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.
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