pCXCL8-1aa   

GtoPdb Ligand ID: 9938

Comment: This is a small peptide that mimics the glycosaminoglycan (GAG) binding domain found in the C-terminal α helix of the CXCL8 cytokine [2]. 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) [3].
The reference article also describes small peptides that interfere with CCL5 and CXCL12γ GAG binding [2].
Chemokine interactions with GAGs localise the chemokines around cell surfaces and the extracellular matrix. This provides a guidance mechanism for leukocyte migration [4]. 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.
2D Structure
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SMILES / InChI / InChIKey
Canonical SMILES NCCCCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)O)CO)CC(=O)N)CCC(=O)O)C)CCCN=C(N)N)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(CCC(=O)O)N)CCCCN)Cc1ccccc1)CC(C)C
Isomeric SMILES NCCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CO)CC(=O)N)CCC(=O)O)C)CCCN=C(N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)N)CCCCN)Cc1ccccc1)CC(C)C
InChI InChI=1S/C53H88N16O17/c1-28(2)24-36(66-50(83)37(25-30-12-5-4-6-13-30)67-47(80)32(14-7-9-21-54)63-44(77)31(56)17-19-41(72)73)49(82)65-33(15-8-10-22-55)46(79)64-34(16-11-23-60-53(58)59)45(78)61-29(3)43(76)62-35(18-20-42(74)75)48(81)68-38(26-40(57)71)51(84)69-39(27-70)52(85)86/h4-6,12-13,28-29,31-39,70H,7-11,14-27,54-56H2,1-3H3,(H2,57,71)(H,61,78)(H,62,76)(H,63,77)(H,64,79)(H,65,82)(H,66,83)(H,67,80)(H,68,81)(H,69,84)(H,72,73)(H,74,75)(H,85,86)(H4,58,59,60)/t29-,31-,32-,33-,34-,35-,36-,37-,38-,39-/m0/s1
InChI Key WAKZDRBORDWUSJ-NXCVNOGKSA-N
Immunopharmacology Comments
pCXCL8-1aa reduces disease severity and serum levels of proinflammatory TNFα in a murine antigen-induced arthritis model, an effect that is mediated by reduced leukocyte activation and infiltration at arthritic sites. Disruption of the cytokine-GAG-cytokine receptor axis is considered as a novel mechanism to be expolited for the development of new classes of anti-inflammatory agents [1].