Glycosaminoglycans as polyelectrolytes.
One of the barriers to understanding structure-property relations for glycosaminoglycans has been the lack of constructive interplay between the principles and methodologies of the life sciences (molecular biology, biochemistry and cell biology) and the physical sciences, particularly in the field of polyelectrolytes. To address this, we first review the similarities and differences between the physicochemical properties of GAGs and other statistical chain polyelectrolytes of both natural and abioitic origin. Since the biofunctionality and regulation of the structures of GAGs is intimately connected with interactions with their cognate proteins, we particularly compare and contrast aspects of protein binding, i.e. effects of both GAGs and other polyelectrolytes on protein stability, protein aggregation and phase behavior. The protein binding affinities and their dependences on pH and ionic strength for the two groups are discussed not only in terms of observable differences, but also with regard to contrasting descriptions of the bound state and the role of electrostatics. We conclude that early studies of the heparin-Antithromin system, proceeding to a large extent through the methods and models of protein chemistry and drug discovery, established not only many enabling precedents but also constraining paradigms. Current studies on heparan sulfate and chondroitin sulfate seem to reflect a more ecumenical view likely to be more compatible with concepts from physical and polymer chemistry.
Seyrek
Emek
E
CNRS, Insitut Charles Sadron, 23 Rue Loess, BP 84047, F-67037 Strasbourg 2, France.
Dubin
Paul
P
D055598:Chemical Phenomena; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011485:Protein Binding; D012996:Solutions; D055672:Static Electricity
D006025:Glycosaminoglycans; D012996:Solutions; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates