Chapter 22
Keratan Sulfates: Structural Investigations Using
Downloaded by PURDUE UNIV on February 25, 2016 | http://pubs.acs.org Publication Date: December 10, 2002 | doi: 10.1021/bk-2003-0834.ch022
N M R Spectroscopy Thomas N. Huckerby, Gavin M. Brown, Robert M. Lauder, and Ian A. Nieduszynski Department of Biological Sciences, IENS, Lancaster University, Bailrigg, Lancaster LA1 4YA, United Kingdom
The application of NMR spectroscopy in the structural study of the families of keratan sulfate glycosaminoglycans is briefly reviewed. Parallel approaches via examinations of intact polymer chains and by isolation and characterization of oligomeric fragments are described.
Introduction Almost fifty years ago, Meyer (1) recognised the polymeric species now named keratan sulfate (KS) as a significant component of cornea. It is an atypical member of the glycosaminoglycan (GAG) family in which there is no acidic residue alternating in the repeat sequence structure with an N-acetylated amino-sugar. The basic motif of the KS polymer is a repeating N-acetylated lactosamine sequence, namely -[Gal(Pl-4)GlcNAc$l-3)-] partially substituted with O-ester sulfate groups located on the pendant methylenes (carbon 6) of the monosaccharide residues. The extent of Gal sulfation is quite varied and relates to the provenance of the KS; at the GlcNAc site, esterification often appears to be complete. n
© 2003 American Chemical Society
In NMR Spectroscopy of Polymers in Solution and in the Solid State; Cheng, H. N., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2002.
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290 Three distinct KS families are now recognised, classified according to the nature of the linkage region' attachment to a protein core. That of type-I, which includes corneal KS, is TV-linked to asparagine through an A^acetylglucosamine extending from the central residue of a triple mannose unit. In the type-Π linkage typical of skeletal KS found, e.g., in articular and non-articular cartilage, nasal septa, and tracheal rings, the connection is through an ^acetylgalactosamine Ch unked to protein through either serine or threonine. Proton NMR reporter group examinations revealed that there were two related types of cartilage KS. That from load-bearing (articular) sites, KS-Π-Α, was more complex (2), containing (£pl-3)-linked fucose and (332-6)-linked N-acetyl-neuraminic (or sialic) acid as well as the (£52-3)-linked sialic acid present also in non-articular KS-II-B. A third class of KS exists in brain tissue; an Oglycosidic linkage connects a GlcNAc(
