Glycosaminoglycans as polyelectrolytes

Seyrek, Emek; Dubin, Paul L.

doi:10.1016/j.cis.2010.03.001

Cited by 59 publications

(80 citation statements)

References 134 publications

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“…To address the role that the multiple negative charges in GAGs play in this process, we compared the effect of GAGs with those of other large non-GAG polysaccharides (charged and neutral). Although the effects of dextran and dextran sulfate have no biological relevance in the context of AL amyloidosis, it has been reported that the physicochemical behavior of GAGs is similar to that of polysaccharides in their role as polyelectrolytes (48).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects on Light Chain Amyloid Formation Depend on Mutations and Type of Glycosaminoglycans

Blancas‐Mejia¹,

Hammernik

Argany³

et al. 2015

Journal of Biological Chemistry

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Background: Extracellular amyloid deposits involve glycosaminoglycans (GAGs). Results: Fibrillation of AL proteins was accelerated by heparan sulfate and inhibited by chondroitin sulfate A. Conclusion: Endogenous GAGs can modulate amyloid formation, and their effect is determined by the amyloidogenic properties of AL proteins studied. Significance: Biologically relevant molecules like GAGs play a major role in the amyloidogenicity of AL proteins.

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Section: Discussionmentioning

confidence: 99%

Differential Effects on Light Chain Amyloid Formation Depend on Mutations and Type of Glycosaminoglycans

Blancas‐Mejia¹,

Hammernik

Argany³

et al. 2015

Journal of Biological Chemistry

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“…In a development of this theme, longer range interactions, which had hitherto been thought to be of relatively minor importance, were then considered in conjunction with modelling studies, supporting the idea that the strongest binding occurs when the heparin/HS polyanion sequences are able to bind the protein in such a way as to optimize both attractive and repulsive electrostatic forces, hence, minimize global energy. Furthermore, simulations showed that there remained some conformational freedom in the bound carbohydrate chain, even when bound with high affinity, and there was evidence of multiple binding sites with different affinities [123]. It is important to attempt to emulate the ionic conditions that pertain physiologically in such investigations because it was observed that, employing ITC [129], only 30% of binding free energy was provided by charge-charge interactions.…”

Section: Fundamentals Of Polysaccharide -Protein Interactions: the Pomentioning

confidence: 99%

“…This is the basis of the approach adopted by Dubin, Seyrek and co-workers, who have applied concepts from polymer and polyelectrolyte chemistry to their analyses [123] as a means of examining the interaction between the highly negatively charged polysaccharides and their protein binding partners, considered as charges in a given space. For example, interaction between AT and heparin bound on an affinity column exhibited a continuous, broad maximum in the apparent binding, rather than showing any abrupt changes (indicative of 'high' and 'low' affinity fractions), as the ionic strength and pH required for elution from an affinity column was varied, suggesting relatively low specificity [124,125].…”

Section: Fundamentals Of Polysaccharide -Protein Interactions: the Pomentioning

confidence: 99%

Heparan sulfate and heparin interactions with proteins

Meneghetti

Hughes

Rudd

et al. 2015

J. R. Soc. Interface.

248

241

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Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissuespecific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure-activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure-activity relationships and regulation will be discussed.

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“…These are flexible polysaccharides, which are decorated with carboxylic acid residues and sulfate groups. Glycosaminoglycans are found on the cell surface and in connective tissue where it functions as an important component of the extracellular matrix [19]. One class in particular which has many different functions are the "heparinoids", which regulate cell -adhesion, -differentiation, -signaling and anti-coagulation [20].…”

Section: Solution Assembled Structures Via Electrostaticsmentioning

confidence: 99%

Polymer Directed Protein Assemblies

Rijn

2013

Polymers

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Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This "biopolymer" directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

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Glycosaminoglycans as polyelectrolytes

Cited by 59 publications

References 134 publications

Differential Effects on Light Chain Amyloid Formation Depend on Mutations and Type of Glycosaminoglycans

Differential Effects on Light Chain Amyloid Formation Depend on Mutations and Type of Glycosaminoglycans

Heparan sulfate and heparin interactions with proteins

Polymer Directed Protein Assemblies

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