Therapeutically targeting protein-glycan interactions.
Glycosylation is the most common form of post-translational modifications by which oligosaccharide side chains are covalently attached to specific residues of the core protein. Especially O-linked glycan structures like the glycosaminoglycans were found to contribute significantly to many (patho-)biological processes like inflammation, coagulation, cancer and viral infections. Glycans exert their function by interacting with proteins thereby changing the structure of the interacting proteins and consequently modulating their function. Given the complex nature of cell-surface and extracellular matrix glycan structures, this therapeutic site has been neglected for a long time, the only exception being the antithrombin III-glycan interaction which has been successfully targeted by unfractionated and low-molecular weight heparins for many decades. Due to the recent breakthrough in the '-ome' sciences, among them proteomics and glycomics, protein-glycan interactions became more amenable for therapeutic approaches so that novel inhibitors of this interaction are currently in preclinical and clinical studies. An overview of current approaches, their advantages and disadvantages, is given and the promising potential of pharmacologically interfering with protein-glycan interactions is highlighted here.
Rek
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ProtAffin Biotechnologie AG, Graz, Austria.
Krenn
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Kungl
A J
AJ
D000818:Animals; D001665:Binding Sites; D002236:Carbohydrate Conformation; D015195:Drug Design; D054794:Glycomics / Q000379:methods; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006031:Glycosylation; D006493:Heparin / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
D006025:Glycosaminoglycans; D008024:Ligands; D011509:Proteoglycans; C036090:heparin proteoglycan; D006493:Heparin