liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Synthesis of inositolphosphoglycans found in Trypanosoma cruzi and development of novel carbohydrate monomolecular layers
Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, synthetic carbohydrate chemistry has been utilized to contribute to the fundamental understanding of three biological relevant areas. These include parasite cell-membrane glycoconjugates, protein-resistant surfaces and antifreeze glycoproteins.

The synthesis of inositolphosphoglycans found in Trypanosoma cruzi, the pathogen of Chagas´ disease, is described. A protected derivative of 6-(2-aminoethyl phosphonic acid)-2-amino-2-deoxy-α-D-glucopyranosyl-(1→6)-D-myo-inositol-1-phosphate was identified as an appropriate acceptor to give a synthetic route to the core oligosaccharide of T. cruzi glycoinositolphospholipids. The assembly of three building blocks accomplished the synthesis of the heptasaccharyl myo-inositol Galf(β1→3)-Manp(α1→2)-[Galf(β1→3)]-Manp(α1→2)-Manp(α1→6)-Manp(α1→4)-6-(2 -aminoethyl phosphonic acid)-GlcNp-(α1→6)-myo-Ins-1-PO4, the glycan of the T. cruzi lipopeptidophosphoglycan.

Carbohydrate self-assembled monolayers (SAMs) on gold were designed, synthesized and characterized to investigate their protein rejecting properties. Synthesis of methylated and non-methylated galactose-terminated alkanethiols provided mixed carbohydrate monomolecular layers. The physiochemical properties of the mixed SAMs were elucidated with ellipsometry, infrared reflection-absorption spectroscopy and contact angle goniometry. The irreversible adsorption of the model proteins fibrinogen and lysozyme was determined with ex-situ ellipsometry. Neither of the proteins adsorbed within a mixed regime corresponding to contact angles of water between 24° and 45°.

A carbohydrate model system mimicking the properties of antifreeze glycoproteins was developed. A Gal(β1→3)-GalNAc terminated 16-mercapto-hexadecanoic acid derivative was synthesized and co-adsorbed with an ethyl-terminated thiol in various proportions to form mixed SAMs on gold. The monolayers were characterized and the antifreeze model system was evaluated by initial ice nucleation studies.

Synthetic routes to protected ethyl 2-deoxy-2-phthalimido-1-β-D-thio-galactosamine derivatives via epimerization of corresponding glucosamine compounds were explored to provide methods in future synthesis of antifreeze glycoproteins and analogues.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2005. , 63 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 980
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-29937Local ID: 15363ISBN: 91-85457-56-6 (print)OAI: oai:DiVA.org:liu-29937DiVA: diva2:250756
Public defence
2005-12-02, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-12-04Bibliographically approved
List of papers
1. Synthesis of the core tetrasaccharide of Trypanosoma cruzi glycoinositolphospholipids: manp(α1→6)-Manp(α1→4)-6-(2-aminoethylphosphonic acid)-GlcNp(α1→6)-myo-Ins-1-PO4
Open this publication in new window or tab >>Synthesis of the core tetrasaccharide of Trypanosoma cruzi glycoinositolphospholipids: manp(α1→6)-Manp(α1→4)-6-(2-aminoethylphosphonic acid)-GlcNp(α1→6)-myo-Ins-1-PO4
2005 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 70, no 18, 7196-7207 p.Article in journal (Refereed) Published
Abstract [en]

Synthesis of the core tetrasaccharide Manp(α1→6)-Manp(α1→4)-6-(2-aminoethylphosphonic acid)-GlcNp(α1→6)-myo-Ins-1-PO4, found in glycoinositolphospholipids of Trypanosoma cruzi parasites, is described. The key building block, 6-O-(2-azido-3-O-benzyl-6-O-((2-benzyloxycarbonylaminoethyl)phosphonic acid benzyl ester)-2-deoxy-α-d-glucopyranosyl)-1-di-O-benzylphosphoryl-4,5-O-isopropylidene-2,3-O-(d-1,7,7-trimethyl[2,2,1]bicyclohept-6-ylidene)-d-myo-inositol, was synthesized using a partially protected glucosyl d-camphorinositolphosphate and a (2-benzyloxycarbonylaminoethyl)phosphonic acid derivative in a regioselective phosphonate esterfication. Elongation with ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-mannopyranosyl-(1→6)-2,3,4-tri-O-benzyl-1-α-d-thiomannopyranoside using dimethyl(methylthio)sulfonium trifluoromethanesulfonate gave a fully protected tetrasaccharide which was successfully deprotected subsequently with sodium methoxide, sodium in liquid ammonia, and aq hydrochloric acid to give title compound.

National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-50423 (URN)10.1021/jo0508595 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
2. Synthesis of the Trypanosoma cruzi LPPG heptasaccharyl myo-inositol
Open this publication in new window or tab >>Synthesis of the Trypanosoma cruzi LPPG heptasaccharyl myo-inositol
2006 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, no 10, 3414-3419 p.Article in journal (Refereed) Published
Abstract [en]

Synthesis of the heptasaccharyl myo-inositol found in Trypanosoma cruzi lipopeptidophosphoglycan was accomplished using a convergent assembly of three building blocks. The target compound is the first complete 2-aminoethyl phosphonic acid substituted glycan related to the glycosylphosphatidylinositol anchor family to be synthesized. The order of assembly enables synthesis of phosphoinositol oligosaccharides related to other glycosylinositolphospholipids in Tr. cruzi, the protozoan parasite causing Chagas' disease, which is endemic in South America.

National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-50263 (URN)10.1021/ja057339b (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
3. Synthesis and self-assembly of galactose-terminated alkanethiols and their ability to resist proteins
Open this publication in new window or tab >>Synthesis and self-assembly of galactose-terminated alkanethiols and their ability to resist proteins
2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 7, 2971-2980 p.Article in journal (Refereed) Published
Abstract [en]

The synthesis of two galactose-terminated alkanethiols with the structural formula X−OC2H5NHCO(CH2)15SH (X = 2,3,4,6-tetra-O-methyl-β-d-Gal or β-d-Gal) is described. Single-component and mixed self-assembled monolayers (SAMs) of the methylated and nonmethylated compounds were prepared on gold and subsequently characterized with ellipsometry, contact angle goniometry, and infraredreflection−absorption spectroscopy. Studies of the irreversible protein adsorption onto the SAMs using ex-situ ellipsometry revealed very low levels of fibrinogen and lysozyme adsorption onto mixed SAMs displaying advancing water contact angles between 24° and 45° and below 45°, respectively. A monomethylated compound (X = 6-O-methyl-β-d-Gal) was also synthesized and assembled on gold. This particular compound was found to possess wettability properties corresponding to the low adsorption regime of the mixed SAMs, and the results from the same set of fibrinogen and lysozyme adsorption experiments showed very low levels of protein adsorption. Our findings suggest that the protein rejecting properties rely on a fine balance between the surface energy and/or hydrogen bond donating/accepting properties of the SAM surface.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-24645 (URN)10.1021/la047203b (DOI)6831 (Local ID)6831 (Archive number)6831 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
4. Mimicking the properties of antifreeze glycoproteins: synthesis and characterization of a model system for ice nucleation and antifreeze studies
Open this publication in new window or tab >>Mimicking the properties of antifreeze glycoproteins: synthesis and characterization of a model system for ice nucleation and antifreeze studies
2005 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 109, no 33, 15849-15859 p.Article in journal (Refereed) Published
Abstract [en]

Synthesis of β-D-Gal-(1 → 3)-β-D-GalNAc coupled to HOC2H4NHCOC15H30SH is described. This compound was coadsorbed at various proportions with C2H5OC2H4NHCOC15H30SH to form statistically mixed self-assembled monolayers (SAMs) on gold in an attempt to mimic the properties of the active domain in antifreeze glycoproteins (AFGPs). The monolayers were characterized by null ellipsometry, contact angle goniometry, X-ray photoelectron spectroscopy, and infrared reflection−absorption spectroscopy. The disaccharide compound adsorbed preferentially, and SAMs prepared at a solution molar ratio >0.3 displayed total wetting. The mixed SAMs showed well-organized alkyl chains up to a disaccharide surface fraction of 0.8. The amount of gauche conformers in the alkyls increased rapidly above this point, and the monolayers became disordered and less densely packed. Furthermore, the generated mixed SAMs were subjected to water vapor at constant relative humidity and the subsequent ice crystallization on a cooled substrate was monitored via an optical microscope. Interestingly, rapid crystallization occurred within a narrow range of temperatures on mixed SAMs with a high disaccharide content, surface fraction >0.3. The reported crystallization temperatures and the ice layer topography were compared with results obtained for a much simpler reference system composed of −OH/−CH3 terminated n-alkanethiols in order to account for changes in topography of the water/ice layer with surface energy. Although preliminary, the obtained results can be useful in the search for the molecular mechanism behind the antifreeze activity of AFGPs.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-14337 (URN)10.1021/jp050752l (DOI)
Available from: 2007-03-16 Created: 2007-03-16 Last updated: 2017-12-13
5. Efficient routes to ethyl-2-deoxy-2-phthalimido-1-β-D-thio-galactosamine derivatives via epimerization of the corresponding glucosamine compounds
Open this publication in new window or tab >>Efficient routes to ethyl-2-deoxy-2-phthalimido-1-β-D-thio-galactosamine derivatives via epimerization of the corresponding glucosamine compounds
2005 (English)In: Journal of carbohydrate chemistry, ISSN 0732-8303, E-ISSN 1532-2327, Vol. 24, no 3, 297-320 p.Article in journal (Refereed) Published
Abstract [en]

Short synthetic routes to protected ethyl 2-deoxy-2-phthalimido-1-β-D- thio-galactosamine derivatives via epimerization of the corresponding glucosamine compounds are described. Starting from D-glucosamine hydrochloride, the epimerizations were performed by displacement of presynthesized triflates with nitrite anions and by an oxidation/reduction route. The latter method involved Moffatt oxidation to the corresponding 4-ketohexoses and subsequent reduction using sodium borohydride/ tetrabutylammonium borohydride, zinc borohydride, or lithium tri-sec-butyl borohydride in THF. The displacement route was found to be the preferred method for epimerization of 3-O-acyl (benzoyl) derivatives. For glucosamine compounds with 3-O-etheral- (allyl or benzyl) and 6-O-benzyl protecting groups, the oxidation/reduction route was the most convenient procedure to achieve corresponding galactosamine compounds. The produced galactosamine derivatives will be useful building blocks in the synthesis of antifreeze glycoproteins substances and analogues thereof.

Keyword
Antifreeze glycoproteins, Epimerization, Galactosamine, Glycosyl donors, Oligosaccharides
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-50380 (URN)10.1081/CAR-200061584 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

Open Access in DiVA

No full text

Authority records BETA

Hederos, Markus

Search in DiVA

By author/editor
Hederos, Markus
By organisation
Department of Physics, Chemistry and BiologyThe Institute of Technology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 125 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf