Abstract:
:The interaction of chemokines and GAGs (glycosaminoglycans) on endothelial surfaces is a crucial step for establishing a chemotactic gradient which leads to the functional presentation of chemokines to their GPCRs (G-protein-coupled receptors) and thus to activation of approaching leucocytes. Based on molecular modelling, biophysical investigations, cell-based and in vivo experiments, we have developed a novel concept for therapeutically interfering with chemokine-GAG interactions, namely dominant-negative chemokine mutants with improved GAG binding affinity and knocked-out GPCR activity. These recombinant proteins displace their wild-type chemokine counterparts from the natural proteoglycan co-receptors without being able to activate leucocytes via GPCRs. Our mutant chemokines therefore represent the first protein-based GAG antagonists with high therapeutic potential in inflammatory diseases.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Potzinger H,Geretti E,Brandner B,Wabitsch V,Piccinini AM,Rek A,Kungl AJdoi
10.1042/BST0340435subject
Has Abstractpub_date
2006-06-01 00:00:00pages
435-7issue
Pt 3eissn
0300-5127issn
1470-8752pii
BST0340435journal_volume
34pub_type
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