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Peter H. Seeberger. Hewitt, Michael Charles, 1975- Massachusetts Institute of Technology. Dept. of Chemistry. Massachusetts Institute of Technology. Department of Chemistry 2005-09-06T21:47:52Z 2005-09-06T21:47:52Z 2002 2002 http://hdl.handle.net/1721.1/27111 56838070 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002. Vita. Includes bibliographical references. The human disease leishmaniasis afflicts over 20 million people worldwide, and is caused by unicellular protozoan parasites. Cell surface carbohydrates are implicated in immune recognition of the parasite by host macrophages. The synthesis of a unique tetrasaccharide found on the parasite cell surface lipophosphoglycan is described. The synthetic material was used to create two novel immungens that are currently being evaluated in an animal model. New methods were also developed for an automated solid-phase synthesis that took a fraction of the time required for the solution-phase synthesis. Malaria kills over 2 million people per year, and is caused by protozoan parasites of the genus Plasmodium. Much of the morbidity and mortality associated with malaria is thought to be due to a toxin released in the host following red blood cell rupture. A glycosylphosphatidylinositol (GPI) anchor of parasite origin was recently identified, and had the properties of a toxin. The synthesis of a modified version of the malarial GPI both in solution and on solid-phase in an automated fashion is described. The synthetic material was attached to a carrier protein and used to immunize mice, who were substantially protected against all aspects of a subsequent challenge by malarial parasites. A new capping protocol for automated solid-phase synthesis is described. A novel fluorous silyl triflate was used to tag deletion sequences that could then be separated from the desired sequence by filtration through fluorous reverse-phase silica gel. Two trisaccharide sequences were synthesized both with and without fluorous capping to demonstrate the effectiveness of the capping protocol. by Michael Charles Hewitt. Ph.D. 225 p. 8998696 bytes 9030751 bytes application/pdf application/pdf en_US Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Chemistry. Solution and solid-phase synthesis of potential carbohydrate vaccines for leishmaniasis and malaria Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="b700fb07-c5c7-4092-b7af-0a4d2de2a445"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>en_US</Language> <Title>Solution and solid-phase synthesis of potential carbohydrate vaccines for leishmaniasis and malaria</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2002</PublicationDate> <Authors> <Author> <DisplayName>Hewitt, Michael Charles, 1975-</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Chemistry.</Keyword> <Abstract>The human disease leishmaniasis afflicts over 20 million people worldwide, and is caused by unicellular protozoan parasites. Cell surface carbohydrates are implicated in immune recognition of the parasite by host macrophages. The synthesis of a unique tetrasaccharide found on the parasite cell surface lipophosphoglycan is described. The synthetic material was used to create two novel immungens that are currently being evaluated in an animal model. New methods were also developed for an automated solid-phase synthesis that took a fraction of the time required for the solution-phase synthesis. Malaria kills over 2 million people per year, and is caused by protozoan parasites of the genus Plasmodium. Much of the morbidity and mortality associated with malaria is thought to be due to a toxin released in the host following red blood cell rupture. A glycosylphosphatidylinositol (GPI) anchor of parasite origin was recently identified, and had the properties of a toxin. The synthesis of a modified version of the malarial GPI both in solution and on solid-phase in an automated fashion is described. The synthetic material was attached to a carrier protein and used to immunize mice, who were substantially protected against all aspects of a subsequent challenge by malarial parasites. A new capping protocol for automated solid-phase synthesis is described. A novel fluorous silyl triflate was used to tag deletion sequences that could then be separated from the desired sequence by filtration through fluorous reverse-phase silica gel. Two trisaccharide sequences were synthesized both with and without fluorous capping to demonstrate the effectiveness of the capping protocol.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>