Glycosaminoglycans (GAGs) and Mimetics—from Basic Science to Applications

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Carbohydrates".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 837

Special Issue Editors


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Guest Editor
1. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA
2. Drug Discovery and Development, Institute for Structural Biology, Virginia Commonwealth University, Richmond, VA 23219, USA
Interests: application of GAGs and GAG mimetics in thrombopoiesis, thrombosis, and inflammation; studies of GAG-protein interactions; photoaffinity labeling technology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
Interests: thrombosis; hemophilia; drug discovery and design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research involving glycosaminoglycans (GAGs), negatively charged biomacromolecules, has gained prominence in recent years. This is in part due to advances in the field, particularly with respect to their isolation, chemical and enzymatic synthesis, and structural characterization. Furthermore, the field has seen an increase in the number of tools available to study the interactions of these molecules with their protein targets, with computational approaches becoming more routine given the challenges with obtaining GAGs in pure form and the increased access to high computing power. The development of molecules that mimic the structure and function of natural GAGs is also witnessing an upsurge. These molecules, which are touted to be easier to synthesize/prepare and be more homogenous, are in some instances thought to be superior to their parent molecules in terms of function. 

Considering the vast potential of GAGs and their mimetics as well as the challenges associated with GAG research, the advancements in this field deserve special attention. As suggested by the title, this Special Issue encompasses fundamental science discoveries and applications of GAGs and GAG-like molecules and will cover topics on 1) the synthesis/preparation of GAGs and GAG-like molecules, 2) the structural characterization of GAGs and GAG-like molecules, 3) the interaction of GAGs and GAG-like molecules with cellular targets, and 4) therapeutic and other applications of GAGs and GAG-like molecules. 

Dr. Daniel Afosah
Dr. Rami A. Al-Horani
Guest Editors

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Keywords

  • Glycosaminoglycans (GAGs)
  • hyaluronan
  • heparin
  • chondroitin sulfate
  • keratan sulfate
  • dermatan sulfate
  • sulfation
  • GAG mimetics
  • GAG-binding proteins

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Published Papers (1 paper)

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Research

23 pages, 4399 KiB  
Article
Dermatan Sulfate Affects the Activation of the Necroptotic Effector MLKL in Breast Cancer Cell Lines via the NFκB Pathway and Rac-Mediated Oxidative Stress
by Grzegorz Wisowski, Adam Pudełko, Monika Paul-Samojedny, Katarzyna Komosińska-Vassev and Ewa M. Koźma
Biomolecules 2024, 14(7), 829; https://doi.org/10.3390/biom14070829 - 10 Jul 2024
Viewed by 497
Abstract
Dermatan sulfate (DS) is a glycosaminoglycan characterized by having a variable structure and wide distribution in animal tissues. We previously demonstrated that some structural variants of DS were able to rapidly induce moderate necroptosis in luminal breast cancer cells when used at a [...] Read more.
Dermatan sulfate (DS) is a glycosaminoglycan characterized by having a variable structure and wide distribution in animal tissues. We previously demonstrated that some structural variants of DS were able to rapidly induce moderate necroptosis in luminal breast cancer cells when used at a high concentration. We have now investigated the mechanisms underlying the DS-mediated activation of the necroptotic executor MLKL using immunofluorescence, Western blotting and pharmacological inhibition. The two main processes, by which DS influences the phosphorylation of MLKL, are the activation of NFκB, which demonstrates a suppressive impact, and the induction of oxidative stress, which has a stimulatory effect. Moreover, the triggering of the redox imbalance by DS occurs via the modulatory influence of this glycosaminoglycan on the rearrangement of the actin cytoskeleton, requiring alterations in the activity of small Rho GTP-ase Rac1. All of these processes that were elicited by DS in luminal breast cancer cells showed a dependence on the structure of this glycan and the type of cancer cells. Furthermore, our results suggest that a major mechanism that is involved in the stimulation of necroptosis in luminal breast cancer cells by high doses of DS is mediated via the effect of this glycan on the activity of adhesion molecules. Full article
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