title: The proteoglycan bikunin has a defined sequence.
abstract: Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge-similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans.
authors: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors: Mellisa
authors: M
authors: Ly
authors: Franklin E
authors: FE
authors: Leach
authors: Tatiana N
authors: TN
authors: Laremore
authors: Toshihiko
authors: T
authors: Toida
authors: I Jonathan
authors: IJ
authors: Amster
authors: Robert J
authors: RJ
authors: Linhardt
mesh_terms: D000510:Alpha-Globulins / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005583:Fourier Analysis; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D011509:Proteoglycans / Q000737:chemistry*
chemical_list: D000510:Alpha-Globulins; D006025:Glycosaminoglycans; D011509:Proteoglycans; C016001:alpha-1-microglobulin