Chemokine-Binding All-D-CLIPS Peptides Identified Using Mirror-Image Phage Display

Chemokines are secreted blood proteins that steer leukocyte migration in the inflammatory response. Neutralization of chemokines is believed to be a beneficial therapeutic strategy for the treatment of inflammation-associated diseases. Proteolytically stable chemokine-binding peptides could be suitable candidates for the development of chemokine-neutralizing agents. Here, we report the mirror-image phage display selection of cyclic all-D-peptides against the C-X-C motif chemokine ligand 8 (CXCL8). Selection yielded structurally diverse all-D-peptides with submicromolar affinity to the target CXCL8 chemokine and different selectivity to related chemokines. Binding of these all-D-peptides caused dissociation of the native CXCL8 dimer and disruption of its binding to GAGs, without an effect on in vitro cell migration. This work demonstrates the example of mirror-image phage display selection of cyclized all-D-peptides and its utility for the development of chemokine-binding agents.