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Structural studies of saccharides and glycopeptides in aqueous solution by 1H NMR spectroscopy

Kindahl, Lill (2003). Structural studies of saccharides and glycopeptides in aqueous solution by 1H NMR spectroscopy. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae. Agraria, 1401-6249 ; 377
ISBN 91-576-6414-5
[Doctoral thesis]

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Abstract

The first part of this thesis describes the use of hydroxy protons for 1H NMR conformational studies of saccharides and small glycopeptide performed in aqueous solution. The conformations of the disaccharide b-D-GlcpNAc-(1®4)-b-D-GlcNAc and of the glycoside b-D-Galp-(1®3)-a-D-GalpNAc-O-Me have been investigated and compared to those of the amino acid linked counterparts b-D-GlcpNAc-(1®4)-b-D-GlcNAc-N-Asn and b-D-Galp-(1®3)-a-D-GalpNAc-O-Ser. For this, the hydroxy proton chemical shifts, vicinal coupling constants, temperature coefficients, exchange rates with water and NOEs were measured. The V[b-D-Galp-(1®3)-a-D-GalpNAc-(1®]THPGY glycopeptide was also investigated. Information about hydrogen bonding interactions and hydration could be obtained. The second part of this thesis describes the 1H NMR studies of the solution conformation of the conotoxin contulakin-G and five analogues. The five analogues had different biological activities, all being less active than contulakin-G. The conformational studies were performed in an attempt to correlate the structure to the activity. Contulakin-G is a 16 amino acid O-glycosylated glycopeptide, which originally was isolated from the venom of the Cone snail Conus geographus. It has the sequence ZSEEGGSNAT*KKPYIL with the disaccharide b-D-Galp-(1®3)-a-D-GalpNAc attached to the threonine residue in position 10. It has entered phase II clinical trials for short-term management of post-operative pain. The five analogues are the non-glycosylated peptide, one glycopeptide with the monosaccharide a-D-GalpNAc attached to Thr10, one with the disaccharide attached at Ser7, and two enantiomeric analogues where the disaccharide was attached at the L-Ser10 and D-ser10 residues, respectively. The NMR studies showed that in all compounds, the peptide predominantly existed in extended conformations. Transient populations of folded conformations were found in the glycosylated peptides. The two most active compounds, contulakin-G, and the (D-Ser10) glycosylated analogue, displayed some similar conformational features.

Authors/Creators:Kindahl, Lill
Title:Structural studies of saccharides and glycopeptides in aqueous solution by 1H NMR spectroscopy
Year of publishing :March 2003
Volume:377
Number of Pages:62
Papers/manuscripts:
NumberReferences
ALLI. Kindahl, L.; Sandström, C.; Norberg, T.; Kenne, L.; ¹H NMR studies of hydroxy protons of Asn- and Ser-linked disaccharides in aqueous solution, J. Carbohydr. Chem. 2000, 19, 1291-1303. II. Kindahl, L.; Sandström, C.; Norberg, T.; Kenne, L.; ¹H NMR studies of hydroxy protons of the V[β-Gal(1→3)-α-GalNAc(1 →O)]THPGY glycopeptide, Carbohydr. Res. 2001, 336, 319-323. III. Kindahl, L.; Sandström, C.; Craig, A. G.; Norberg, T.; Kenne, L.; ¹H NMR studies on the solution conformation of Contulakin-G and analogues, Can. J. Chem. 2002, 80, 1022-1031. IV. Kindahl, L.; Sandström, C.; Craig, A. G.; Norberg, T.; Kenne, L.; Structural studies by ¹H NMR of the [L-Ser10] and [D-Ser10] analogues of contulakin-G, manuscript.
Place of Publication:Uppsala
ISBN for printed version:91-576-6414-5
ISSN:1401-6249
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X50 Chemistry
Subjects:Not in use, please see Agris categories
Agrovoc terms:carbohydrates, peptides, solutions, hydrogen, spectrometry
Keywords:hydroxy proton, contulakin-G, conotoxin, conformational analysis, hydrogen bond, O-glycosylation
URN:NBN:urn:nbn:se:slu:epsilon-23
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-23
ID Code:194
Department:(NL, NJ) > Dept. of Chemistry (until 131231)
Deposited By: Lill Kindahl
Deposited On:18 Mar 2003 00:00
Metadata Last Modified:02 Dec 2014 10:02

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