Targeting the Atypical Chemokine Receptor ACKR3/CXCR7 for the treatment of cancer and other diseases

摘要: One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 expressed on many types, including breast glioblastoma, binds endogenous ligands SDF1/CXCL12 ITAC/CXCL11. A 20 amino acid region N-terminus was synthesized targeted with NEB PhD-7 Phage Display Peptide Library. Twenty-nine phages were isolated heptapeptide inserts sequenced; these, 23 sequences unique. 3D molecular model created for by mutating corresponding crystal structure CXCR4 bound SDF1/CXCL12. ClustalW alignment performed each peptide sequence using entire as template. 23-peptide showed similarity to three distinct regions molecule. made phage visually identify potential areas steric interference peptides that simulated CXCL12 not contact receptor's N-terminus. An ELISA analysis relative binding affinity between identified 9 statistically significant results. candidate pool further reduced 3 based their versus no target present or a scrambled negative control peptide. results clearly show protocol can be used chosen, P20, P3, P9, effect viability proliferation upon exposure MCF-7 U87-MG cells. Membrane binding, colocalization, cellular uptake confirmed whole-cell confocal microscopy. recovered did activate receptor Beta-Arrestin recruitment assay. data shows from display are viable candidates cells delivering material them.