This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Chondroitin/dermatan sulfate (CS/DS) chains consist of domains differentiated by sulfation and epimerization patterns expressed in a tissue and cell-type specific manner. One of the long term goals in the group has been to extend the length of the CS/DS chains as far as possible, toward the end of intact chain analysis. We have observed previously that the abundances of product ions generated from CS/DS oligosaccharides depends on the glycoforms present. This may readily be determined using purified standards corresponding to CS type A (GlcA-GalNAc4S)n, type B (IdoA-GalNAc4S)n and type C (GlcA-GalNAc6S)n. Typically, one ion diagnostic for each glycoform is observed in a tandem mass spectrum. For a degree of polymerization (dp) 12 oligosaccharide, the Y3 ion is most abundant for CS type A, the Y9 ion for type B and the M-SO3 ion for type C. As the size of the oligosaccharide increases, the same general trend is observed with one ion diagnostic for each glycoform. It is of interest to be able to differentiate the presence of more than one structural domain in an extended CS/DS oligosaccharide. Thus, it is necessary to determine the structural epitopes to which a given diagnostic product are sensitive. Towards this end, we subjected all MS2 B and Y product ions to MS3 for CS/DS chains of dp10-16. The results showed that MS3 dissociation of Y-type ion formed product ions the abundances of which depended on the CS/DS glycoform. The pattern of MS3 product ions was useful for defining the structural epitopes to which the diagnostic product ions are sensitive. The MS3 product ions generated from B-type ions showed far less discriminatory value for CS/DS glycoforms. Progress update: The results of this work have been accepted for publication in International Journal of Mass Spectrometry

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