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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Ly M,Leach FE 3rd,Laremore TN,Toida T,Amster IJ,Linhardt RJdoi
10.1038/nchembio.673subject
Has Abstractpub_date
2011-10-09 00:00:00pages
827-33issue
11eissn
1552-4450issn
1552-4469pii
nchembio.673journal_volume
7pub_type
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