Glycosaminoglycan origin and structure revealed by multivariate analysis of NMR and CD spectra.
Principal component analysis (PCA) is a method of simplifying complex datasets to generate a lower number of parameters, while retaining the essential differences and allowing objective comparison of large numbers of datasets. Glycosaminoglycans (GAGs) are a class of linear sulfated carbohydrates with diverse sequences and consequent complex conformation and structure. Here, PCA is applied to three problems in GAG research: (i) distinguishing origins of heparin preparations, (ii) structural analysis of heparin derivatives, and (iii) classification of chondroitin sulfates (CS). The results revealed the following. (i) PCA of heparin (13)C NMR spectra allowed their origins to be distinguished and structural differences were identified. (ii) Analysis of the information-rich (1)H and (13)C NMR spectra of a series of systematically modified heparin derivatives uncovered underlying properties. These included the presence of interactions between residues, providing evidence that a degree of degeneracy exists in linkage geometry and that a different degree of variability exists for the two types of glycosidic linkage. The relative sensitivity of each position (C or H nucleus) in the disaccharide repeating unit to changes in O-, N-sulfation and N-acetylation was also revealed. (iii) Analysis of the (1)H NMR and CD spectra of a series of CS samples from different origins allowed their structural classification and highlighted the power of employing complementary spectroscopic methods in concert with PCA.
Rudd
Timothy R
TR
School of Biological Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.
Skidmore
Mark A
MA
Guimond
Scott E
SE
Cosentino
Cesare
C
Torri
Giangiacomo
G
Fernig
David G
DG
Lauder
Robert M
RM
Guerrini
Marco
M
Yates
Edwin A
EA
D002809:Chondroitin Sulfates / Q000737:chemistry*; D002942:Circular Dichroism; D006025:Glycosaminoglycans / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D025341:Principal Component Analysis
D006025:Glycosaminoglycans; D006493:Heparin; D002809:Chondroitin Sulfates