pCXCL8-1aa   Click here for help

GtoPdb Ligand ID: 9938

Immunopharmacology Ligand
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 [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
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
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
References
1. Falsone A, Wabitsch V, Geretti E, Potzinger H, Gerlza T, Robinson J, Adage T, Teixeira MM, Kungl AJ. (2013)
Designing CXCL8-based decoy proteins with strong anti-inflammatory activity in vivo.
Biosci Rep, 33 (5). [PMID:23919527]
2. McNaughton EF, Eustace AD, King S, Sessions RB, Kay A, Farris M, Broadbridge R, Kehoe O, Kungl AJ, Middleton J. (2018)
Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis.
J Immunol, 200 (9): 3201-3217. [PMID:29572348]
3. Proudfoot AE, Fritchley S, Borlat F, Shaw JP, Vilbois F, Zwahlen C, Trkola A, Marchant D, Clapham PR, Wells TN. (2001)
The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity.
J Biol Chem, 276 (14): 10620-6. [PMID:11116158]
4. Proudfoot AEI, Johnson Z, Bonvin P, Handel TM. (2017)
Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.
Pharmaceuticals (Basel), 10 (3). [PMID:28792472]