Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides

Bibliographic Details
Main Author:	Eradi, Pradheep
Language:	English
Published:	University of Toledo / OhioLINK 2019
Subjects:	Chemistry Organic Chemistry Zwitterionic polysaccharides polysaccharide A PS A1 Bacteroides fragilis Total synthesis of PS A1 repeating unit antigen fragments
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556557615511811

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-toledo15565576155118112021-08-03T07:10:50Z Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides Eradi, Pradheep Chemistry Organic Chemistry Zwitterionic polysaccharides polysaccharide A PS A1 Bacteroides fragilis Total synthesis of PS A1 repeating unit antigen fragments Zwitterionic polysaccharides (ZPSs) are a relatively new class of carbohydrate antigens, with a paradigm shifting property; they can activate CD4+ T-cells in the absence of lipids, peptide(s) or protein(s) upon MHC class II presentation. Up until now, various anaerobic bacteria are known to express ZPSs, for example, PS A1, PS A2 and PS B (Bacteroides fragilis), Sp1 (Streptococcus pneumoniae), CP5 and CP8 (Staphylococcus aureus) and O-chain antigen (Morganella morgani). Among all the afore mentioned ZPSs, Sp1 and PS A1 polysaccharides were the prime focus of research for the past few decades and their biological properties are very well-understood. Polysaccharide A1 (PS A1), the most potent and abundantly expressed in the capsular polysaccharide complex (CPC) of B. fragilis, is known for its dual immunomodulatory properties based on the physiological location in the host. PS A1 has been used as a carrier for various tumor antigens like Tn, TF and STn, opening a platform for entirely carbohydrate-based vaccines and the respective immunological outcomes are now known to be very promising. Biological isolation of PS A1 through tedious work-up procedures leads to heterogeneous material in length, and is not suitable for the precise mechanistic studies for T-cell activation and beyond. A well-thought and executed chemical synthesis can provide completely defined synthetic PS A1 antigen fragments and can be used as molecular probes for the study of T-cell activation and other important biological processes. In order to determine the immunologically active epitope of PS A1, the first total synthesis of PS A1 repeating unit with alternating charges on adjacent sugars was accomplished using a linear glycosylation strategy and biological studies are currently in progress. Synthesis of oligomeric length PS A1 antigen fragments were up-taken to determine whether the immunologically active T-cell epitope of PS A1 is a sequential or conformational epitope. Pure, well-defined synthetic PS A1 fragments will help in understanding the precise T-cell activation mechanism and provide unprecedented biological data through in vitro and in vivo studies; access to crystal structures of MHC II proteins with PS A1 synthetic antigen fragment will tremendously help in understanding the nature of critical interactions involved between the peptide and sugar residues. The outcome of the above mentioned studies will lead to the development of completely defined, entirely carbohydrate-based “synthetic vaccine candidate” and also provides opportunity to develop new synthetic PS A1 analogues based on the structure-activity relationship. 2019-08-28 English text University of Toledo / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556557615511811 http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556557615511811 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Chemistry Organic Chemistry Zwitterionic polysaccharides polysaccharide A PS A1 Bacteroides fragilis Total synthesis of PS A1 repeating unit antigen fragments
spellingShingle	Chemistry Organic Chemistry Zwitterionic polysaccharides polysaccharide A PS A1 Bacteroides fragilis Total synthesis of PS A1 repeating unit antigen fragments Eradi, Pradheep Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
author	Eradi, Pradheep
author_facet	Eradi, Pradheep
author_sort	Eradi, Pradheep
title	Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
title_short	Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
title_full	Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
title_fullStr	Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
title_full_unstemmed	Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides
title_sort	total synthesis of zwitterionic bacterial polysaccharide (ps a1) antigen fragments from b. fragilis atcc 25285/nctc 9343 with alternating charges on adjacent monosaccharides
publisher	University of Toledo / OhioLINK
publishDate	2019
url	http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556557615511811
work_keys_str_mv	AT eradipradheep totalsynthesisofzwitterionicbacterialpolysaccharidepsa1antigenfragmentsfrombfragilisatcc25285nctc9343withalternatingchargesonadjacentmonosaccharides
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Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides

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