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

Area of Science:

• Immunology
• Biochemistry
• Drug Discovery

Background:

• Chemokines, such as C-X-C motif chemokine ligand 8 (CXCL8), are crucial for leukocyte migration during inflammation.
• Neutralizing chemokines is a potential therapeutic strategy for inflammatory conditions.
• Proteolytically stable peptides offer a promising avenue for developing chemokine-binding agents.

Purpose of the Study:

• To develop novel, stable chemokine-binding peptides using mirror-image phage display.
• To investigate the binding affinity and selectivity of all-D-peptides against CXCL8.
• To assess the functional impact of these peptides on CXCL8 activity.

Main Methods:

• Mirror-image phage display selection was employed to identify cyclic all-D-peptides targeting CXCL8.
• Binding affinity and selectivity of selected peptides were characterized.
• The effect of peptide binding on CXCL8 dimerization and glycosaminoglycan (GAG) binding was evaluated.

Main Results:

• Structurally diverse all-D-peptides with submicromolar affinity for CXCL8 were successfully selected.
• Selected peptides demonstrated varying selectivity towards related chemokines.
• Peptide binding led to the dissociation of native CXCL8 dimers and disrupted CXCL8-GAG interactions.

Conclusions:

• Mirror-image phage display is effective for selecting cyclic all-D-peptides against chemokines.
• Developed all-D-peptides can neutralize CXCL8 by disrupting its structure and interactions.
• These findings support the potential of all-D-peptides as therapeutic agents for chemokine-mediated inflammatory diseases.