Heparan sulfate-binding chemokines (HS-binding chemokines)

Heparan sulfate-binding chemokines are a functional class of signaling proteins that require interaction with glycosaminoglycans (GAGs) to exert their full biological activity in vivo (Proudfoot et al., 2003, PNAS). These chemokines bind to heparan sulfate chains on proteoglycans located on the vascular endothelium and in the extracellular matrix, a process essential for the formation of haptotactic gradients that guide leukocyte migration (Monneau et al., 2016, Frontiers in Immunology). Beyond gradient formation, heparan sulfate protects chemokines from proteolytic degradation and facilitates their presentation to signaling receptors (Handel et al., 2005, Annual Review of Biochemistry). In diseases such as cancer and chronic inflammation, these chemokines are often overexpressed, leading to pathological cell recruitment, angiogenesis, and metastasis. Therapeutic interventions aim to disrupt the chemokine-GAG interface using small molecule inhibitors, heparin mimetics like Muparfostat, or specialized aptamers like Olaptesed pegol (Noxxon Pharma). Such strategies effectively neutralize the chemokine's ability to recruit cells without necessarily blocking the receptor-binding site directly, offering a nuanced approach to treating inflammatory and oncological conditions.

Other names

Glycosaminoglycan-binding chemokinesGAG-binding chemokinesHeparin-binding chemokinesHeparan sulfate-interacting cytokines

Inhibition of chemokine-glycosaminoglycan (GAG) interactions to disrupt haptotactic gradients and prevent leukocyte recruitment to sites of inflammation or tumor microenvironments.