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Compound class: Peptide or derivative
Comment: This is a small peptide that mimics the glycosaminoglycan (GAG) binding domain found in the C-terminal α helix of the CXCL8 cytokine . It competes with CXCL8 for binding to GAGs, and by interfering in this interaction, reduces CXCL8-mediated inflammatory responses (leukocyte activation and extravasation to inflammatory sites).
The archetypal GAG-binding motif on CXC chemokines takes the form XBBBXXBX (where B = a basic amino acid and X = any nonbasic amino acid) .
The reference article also describes small peptides that interfere with CCL5 and CXCL12γ GAG binding .
Chemokine interactions with GAGs localise the chemokines around cell surfaces and the extracellular matrix. This provides a guidance mechanism for leukocyte migration . Disrupting this guidance mechanism is predicted to produce anti-inflammatory effects, by reducing the ability of pro-inflammatory cells to migrate to sites of inflammation in response to cytokine signals.