Synthesis and Test of Peptides and Peptoids for the Inhibition of Cytokines (English shop)

Preview

Table of Contents, PDF (50 KB)
Extract, PDF (480 KB)

This work describes the identification and characterization of chemokine ligands of the compound classes of peptides and peptoids. In the first part of this work, a model of the receptor-ligand complex of the chemokine CXCL8 and its receptor CXCR1 was generated by flexible protein-protein docking. The model confirmed the possibility of an interaction between the ELR motif of CXCL8 and the extracellular domains of CXCR1, which was previously suggested by the literature. Based on this model, a peptide was designed by connecting two sequence motifs of CXCR1 in an attempt to mimic the receptor binding site. The peptide was determined to bind CXCL8 with an affinity of 500 nM and was found to inhibit CXCL8-induced migration of human neutrophil granulocytes. In the second part of this work, one-bead-one-compound (OBOC) libraries of peptoids on TentaGel resin were tested for their ability to bind fluorescently labelled CXCL8. By optimising screening parameters and by analysing microscopy images of the resin in two different fluorescence channels, 18 peptoids were identified that bind CXCL8 with micromolar affinities.