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Synthesis and analysis of carbohydrates related to bacterial polysaccharides
Stockholm University, Faculty of Science, Department of Organic Chemistry.ORCID iD: 0000-0001-5651-3858
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The outer surface of bacteria is composed of around 75% carbohydrates, which are vital for the bacteria to survive and communicate with the host biological system. The thesis discusses different properties of carbohydrates that are essential for understanding the bacterial behavior in biological systems. The first three chapters give an overview of carbohydrates.

The fourth chapter discusses the synthesis of four amide-substituted 3,6-dideoxy-α-D-galactopyranosides, namely, methyl α-3,6-dideoxy-3-formamido-, acetamido-, (R)-3-hydroxybutyramido-, and (4-hydroxybutyramido)-D-galactopyranoside. These sugars were found as components of some bacterial O-antigens; the study is a step toward the synthesis of oligosaccharides that contain them. The fifth chapter describes the exchange kinetics of the formyl and acetyl derivatives that were synthesized. Both of them have two conformational states for the amide side-chain. 13C-NMR saturation transfer experiments are utilized for these measurements to reveal more about their properties in solution.

In chaptr six, NMR and conformational analysis of oligosaccharides related to the O-antigen of Yersinia enterocolitica O:3 bacteria were carried out to obtain more information regarding their 3D structure.

Chapter seven is focusing on the development of CASPER, a program for rapid assignment of 1H- and 13C-NMR chemical shifts of bacterial lipopolysaccharides, by adding more sugars into its database and testing it for naturally occurring LPS as well as extending the scope for synthetic carbohydrates, which is planned to be developed further in the future.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University , 2018. , p. 53
Keywords [en]
carbohydrates, synthesis, conformation, NMR, O-antigen, computer-assisted structure elucidation
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-154449ISBN: 978-91-7797-216-7 (print)ISBN: 978-91-7797-217-4 (electronic)OAI: oai:DiVA.org:su-154449DiVA, id: diva2:1193800
Public defence
2018-05-15, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2018-04-20 Created: 2018-03-27 Last updated: 2018-04-23Bibliographically approved
List of papers
1. Synthesis of methyl 3-amino-3,6-dideoxy-alpha-d-galactopyranoside carrying different amide substituents
Open this publication in new window or tab >>Synthesis of methyl 3-amino-3,6-dideoxy-alpha-d-galactopyranoside carrying different amide substituents
2013 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 3, no 45, p. 23090-23097Article in journal (Refereed) Published
Abstract [en]

Bacterial polysaccharides may contain rare sugars of different stereochemistry and diverse functional groups; the repertoire can be further extended by varying the exocyclic substituents. Synthesis of four monosaccharides is described utilizing a suitably protected key intermediate obtained by regioselective acetal ring-opening reduction, dexoygenation at C6, alcohol oxidation at C3 followed by formation of an oxime, which was stereoselectively reduced by samarium diiodide to give a 3-amino-derivative having the desired galacto-configuration. Subsequent functionalization was performed resulting in one to four carbon atoms in the amide substituent.

National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-97407 (URN)10.1039/c3ra45092a (DOI)000326395800056 ()
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note

AuthorCount:3;

Available from: 2013-12-11 Created: 2013-12-09 Last updated: 2018-03-27Bibliographically approved
2. Conformational Dynamics and Exchange Kinetics of N-Formyl and N-Acetyl Groups Substituting 3-Amino-3,6-dideoxy-alpha-D-galactopyranose, a Sugar Found in Bacterial O-Antigen Polysaccharides
Open this publication in new window or tab >>Conformational Dynamics and Exchange Kinetics of N-Formyl and N-Acetyl Groups Substituting 3-Amino-3,6-dideoxy-alpha-D-galactopyranose, a Sugar Found in Bacterial O-Antigen Polysaccharides
2017 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 121, no 41, p. 9487-9497Article in journal (Refereed) Published
Abstract [en]

Three dimensional shape and conformation of. carbohydrates are important factors in molecular recognition events and the N-acetyl group of a monosaccharide residue can function as a conformational gatekeeper whereby it influences the overall shape of the oligosaccharide. NMR spectroscopy and quantum mechanics (QM) calculations are used herein to investigate both the conformational preferences and the dynamic behavior of N-acetyl and N-formyl substituents of 3-amino-3,6-dideoxy-alpha-D-galactopyranose, a sugar and substitution pattern found in bacterial O-antigen polysaccharides. QM calculations suggest that the amide oxygen can be involved in hydrogen bonding with the axial OH4 group primarily but also with the equatorial OH2 group. However, an NMR J coupling analysis indicates that the 01 torsion angle, adjacent to the sugar ring, prefers an ap conformation where conformations <180 degrees also are accessible, but does not allow for intramolecular hydrogen bonding. In the formyl-substituted compound (4)J(HH) coupling constants to the exo-cyclic group were detected and analyzed. A van't Hoff analysis revealed that the trans conformation at the amide bond is favored by Delta G degrees approximate to - 0.8 kcal.mol(-1) in the formyl-containing compound and with Delta G degrees approximate to -2.5 kcal.mol(-1) when the N-acetyl group is the substituent. In both cases the enthalpic term dominates to the free energy, irrespective of water or DMSO as solvent, with only a small contribution from the entropic term. The cis-trans isomerization of the theta(2) torsion angle, centered at the amide bond, was also investigated by employing H-1 NMR line shape analysis and C-13 NMR saturation transfer experiments. The extracted transition rate constants were utilized to calculate transition energy barriers that were found to be about 20 kcal.mol(-1) in both DMSO-d(6) and D2O. Enthalpy had a higher contribution to the energy barriers in DMSO-d(6) compared to in D2O, where entropy compensated for the loss of enthalpy.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-148998 (URN)10.1021/acs.jpcb.7b05611 (DOI)000413617800001 ()28933544 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note

Open Access 2019-12-01

Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2019-09-06Bibliographically approved
3. Synthesis of β-(1 -> 2)-Linked 6-Deoxy-L-altropyranose Oligosaccharides via Gold(I)-Catalyzed Glycosylation of an ortho-Hexynylbenzoate Donor
Open this publication in new window or tab >>Synthesis of β-(1 -> 2)-Linked 6-Deoxy-L-altropyranose Oligosaccharides via Gold(I)-Catalyzed Glycosylation of an ortho-Hexynylbenzoate Donor
Show others...
2017 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, no 6, p. 3062-3071Article in journal (Refereed) Published
Abstract [en]

The ss-(1 -> 2)-linked 6-deoxy-L-altropyranose di- to pentasaccharides 2-5, relevant to the O-antigen of the infectious Yersinia enterocolitica 0:3, were synthesized for the first time. The challenging 1,2-cis-altropyranosyl linkage was assembled effectively via glycosylation with 2-O-benzyl-3,4-di-O-benzoyl-6-deoxy-L-altropyranosyl ortho-hexynylbenzoate (7) under the catalysis of PPh3AuNTf2. NMR and molecular modeling studies showed that the pentasaccharide (5) adopted a left-handed helical conformation. [GRAPHICS]

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-142654 (URN)10.1021/acs.joc.7b00057 (DOI)000397077500026 ()28230982 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2019-02-06Bibliographically approved
4. Complete 1H and 13C NMR chemical shift assignments of mono- to tetrasaccharides as basis for NMR chemical shift predictions of oligo- and polysaccharides using the computer program CASPER
Open this publication in new window or tab >>Complete 1H and 13C NMR chemical shift assignments of mono- to tetrasaccharides as basis for NMR chemical shift predictions of oligo- and polysaccharides using the computer program CASPER
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-146864 (URN)
Available from: 2017-09-13 Created: 2017-09-13 Last updated: 2018-03-27Bibliographically approved

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