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Synthesis of L. Major Derived Carboh...

Rintelmann, Chelsea Lynnette.

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Synthesis of L. Major Derived Carbohydrate Chemical Probes and a Polydivergently Protected High-Mannose Type N-Glycan Core Pentasaccharide.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Synthesis of L. Major Derived Carbohydrate Chemical Probes and a Polydivergently Protected High-Mannose Type N-Glycan Core Pentasaccharide./
Author:	Rintelmann, Chelsea Lynnette.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	301 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
Contained By:	Dissertations Abstracts International81-10B.
Subject:	Organic chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27743269
ISBN:	9781658490580

Synthesis of L. Major Derived Carbohydrate Chemical Probes and a Polydivergently Protected High-Mannose Type N-Glycan Core Pentasaccharide.
Rintelmann, Chelsea Lynnette.

Synthesis of L. Major Derived Carbohydrate Chemical Probes and a Polydivergently Protected High-Mannose Type N-Glycan Core Pentasaccharide. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 301 p.

Source: Dissertations Abstracts International, Volume: 81-10, Section: B.

Thesis (Ph.D.)--Indiana University, 2020.

This item must not be sold to any third party vendors.

Glycans possess a wide array of biological functions from cellular signaling, identification and processing, to pathogenesis. Despite these molecules' high structural homogeneity, subtle changes in the glycan structure modulates their biological effects. Identification of these biological molecules from natural sources will assist with targeted therapeutic development and disease diagnosis. The high structural homogeneity however impedes the purification and characterization of these molecules from isolates. Targeted chemical synthesis of structurally defined glycans will provide standards for identification and biological analysis.Three carbohydrate chemical probes were strategically synthesized to characterize the immunosuppressive mechanisms of in vitro and in vivo pathogeneses of L. major-induced leishmaniasis. The synthesized probes were designed to mimic the Leishmania pathogen through glycan identity, size, and multivalency. Assessment of these truncated pathogenic glycan probes resulted in promising therapeutic potential for vaccine and adjuvant development by inducing adaptive immunity and pathogen clearance.High-mannose type N-glycans are important targets for therapeutic development, but are difficult to synthesize selectively due to their high homogeneity in structure. An orthogonally protected core N-glycan trisaccharide acceptor precursor structure was synthesized for applications in polydivergent library synthesis of asymmetrically branched high- mannose type N-glycans. Six differentially protected mannose and glucosamine monosaccharides were prepared in 30 total synthetic steps in a convergent manner from common intermediates. The protecting groups were strategically selected to provide high regio- and stereo-selective glycosylations to construct asymmetric target structures. Preparation of these differentially protected monosaccharide components were optimized through omission of alkylstannanes and substitution with a benign iron catalyst. Synthesis of the difficult beta-mannose linkage was achieved through application of Yu's Au(I)-catalyzed beta-mannosylation through convergent and linear syntheses of the core trisaccharide. The synthesized trisaccharide and pentasaccharide will assist in targeted synthesis of libraries of high-mannose N-glycans for further biological and therapeutic analysis.

ISBN: 9781658490580Subjects--Topical Terms:

523952
Organic chemistry.
Subjects--Index Terms:

Carbohydrates

Synthesis of L. Major Derived Carbohydrate Chemical Probes and a Polydivergently Protected High-Mannose Type N-Glycan Core Pentasaccharide.
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300 $a 301 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
500 $a Advisor: Pohl, Nicola L. B.
502 $a Thesis (Ph.D.)--Indiana University, 2020.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Glycans possess a wide array of biological functions from cellular signaling, identification and processing, to pathogenesis. Despite these molecules' high structural homogeneity, subtle changes in the glycan structure modulates their biological effects. Identification of these biological molecules from natural sources will assist with targeted therapeutic development and disease diagnosis. The high structural homogeneity however impedes the purification and characterization of these molecules from isolates. Targeted chemical synthesis of structurally defined glycans will provide standards for identification and biological analysis.Three carbohydrate chemical probes were strategically synthesized to characterize the immunosuppressive mechanisms of in vitro and in vivo pathogeneses of L. major-induced leishmaniasis. The synthesized probes were designed to mimic the Leishmania pathogen through glycan identity, size, and multivalency. Assessment of these truncated pathogenic glycan probes resulted in promising therapeutic potential for vaccine and adjuvant development by inducing adaptive immunity and pathogen clearance.High-mannose type N-glycans are important targets for therapeutic development, but are difficult to synthesize selectively due to their high homogeneity in structure. An orthogonally protected core N-glycan trisaccharide acceptor precursor structure was synthesized for applications in polydivergent library synthesis of asymmetrically branched high- mannose type N-glycans. Six differentially protected mannose and glucosamine monosaccharides were prepared in 30 total synthetic steps in a convergent manner from common intermediates. The protecting groups were strategically selected to provide high regio- and stereo-selective glycosylations to construct asymmetric target structures. Preparation of these differentially protected monosaccharide components were optimized through omission of alkylstannanes and substitution with a benign iron catalyst. Synthesis of the difficult beta-mannose linkage was achieved through application of Yu's Au(I)-catalyzed beta-mannosylation through convergent and linear syntheses of the core trisaccharide. The synthesized trisaccharide and pentasaccharide will assist in targeted synthesis of libraries of high-mannose N-glycans for further biological and therapeutic analysis.
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653 $a Chemical probes
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653 $a Total synthesis
653 $a Vaccine
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