1. Development of a novel ELISA for the testing of glycobioconjugates as anti-HIV agents 2. Synthesis of potential inhibitors of the HIV entry mechanism 3. Probing the secondary structural characteristics of oligosaccharides utilizing circular dichroism

Persistent Link:
http://hdl.handle.net/10150/283988
Title:
1. Development of a novel ELISA for the testing of glycobioconjugates as anti-HIV agents 2. Synthesis of potential inhibitors of the HIV entry mechanism 3. Probing the secondary structural characteristics of oligosaccharides utilizing circular dichroism
Author:
McReynolds, Kathrine Dawn
Issue Date:
1999
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
AIDS, or acquired immunodeficiency syndrome, is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus that is capable of rapid genetic mutation, which makes the virus and the disease difficult to treat. Several drug therapies are currently available, in the form of viral enzyme inhibitors. Other inhibitors of the viral entry and replication process are being investigated to enhance the drug therapy arsenal. Our research has focused on the development of HIV entry inhibitors. We are working towards the development of novel carbohydrate-based agents that are capable of binding the gp120 protein on the viral surface, such that viral entry into an uninfected host cell is prevented. In order for our research to progress, a qualitative method by which our synthetic compounds could be evaluated for gp120 binding was sought. We have developed a unique ELISA (enzyme-linked immunosorbent assay) that indicates whether or not a compound has binding affinity for the viral protein. A TIRF (total internal reflection fluorescence) microscopy method, has been developed as part of a collaborative effort with the laboratories of Professors Saavedra and O'Brien, to assess active compounds for quantitative equilibrium binding constants to gp120. We have synthesized several carbohydrate-based molecules targeted to one or more of the binding sites on the surface of gp120; the galactosylceramide site, the V3 loop, and the CD4 binding site. Utilizing both the ELISA and TIRF methods, we have succeeded in probing the binding profile of gp120. Circular dichroism studies have also been employed to evaluate the secondary structural characteristics of oligomeric carbohydrate materials. Molecules with helical properties have potential as CD4 binding site inhibitors. The long term goals of this project involve the synthesis and gp120 binding evaluation of novel carbohydrate-based materials to serve as entry inhibitors of the HIV replication process. A possible application of this project lies in the development of compounds capable of binding to more than one site on the protein. A variation of this goal involves the tethering of various compounds with specificities to different sites on gp120, for the purpose of inhibiting multiple binding sites on the protein.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Chemistry, Organic.; Chemistry, Pharmaceutical.; Health Sciences, Pathology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Gervay-Hague, Jacquelyn

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.title1. Development of a novel ELISA for the testing of glycobioconjugates as anti-HIV agents 2. Synthesis of potential inhibitors of the HIV entry mechanism 3. Probing the secondary structural characteristics of oligosaccharides utilizing circular dichroismen_US
dc.creatorMcReynolds, Kathrine Dawnen_US
dc.contributor.authorMcReynolds, Kathrine Dawnen_US
dc.date.issued1999en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractAIDS, or acquired immunodeficiency syndrome, is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus that is capable of rapid genetic mutation, which makes the virus and the disease difficult to treat. Several drug therapies are currently available, in the form of viral enzyme inhibitors. Other inhibitors of the viral entry and replication process are being investigated to enhance the drug therapy arsenal. Our research has focused on the development of HIV entry inhibitors. We are working towards the development of novel carbohydrate-based agents that are capable of binding the gp120 protein on the viral surface, such that viral entry into an uninfected host cell is prevented. In order for our research to progress, a qualitative method by which our synthetic compounds could be evaluated for gp120 binding was sought. We have developed a unique ELISA (enzyme-linked immunosorbent assay) that indicates whether or not a compound has binding affinity for the viral protein. A TIRF (total internal reflection fluorescence) microscopy method, has been developed as part of a collaborative effort with the laboratories of Professors Saavedra and O'Brien, to assess active compounds for quantitative equilibrium binding constants to gp120. We have synthesized several carbohydrate-based molecules targeted to one or more of the binding sites on the surface of gp120; the galactosylceramide site, the V3 loop, and the CD4 binding site. Utilizing both the ELISA and TIRF methods, we have succeeded in probing the binding profile of gp120. Circular dichroism studies have also been employed to evaluate the secondary structural characteristics of oligomeric carbohydrate materials. Molecules with helical properties have potential as CD4 binding site inhibitors. The long term goals of this project involve the synthesis and gp120 binding evaluation of novel carbohydrate-based materials to serve as entry inhibitors of the HIV replication process. A possible application of this project lies in the development of compounds capable of binding to more than one site on the protein. A variation of this goal involves the tethering of various compounds with specificities to different sites on gp120, for the purpose of inhibiting multiple binding sites on the protein.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Organic.en_US
dc.subjectChemistry, Pharmaceutical.en_US
dc.subjectHealth Sciences, Pathology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGervay-Hague, Jacquelynen_US
dc.identifier.proquest9946872en_US
dc.identifier.bibrecord.b39920434en_US
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