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

TL;DR

Researchers developed stable peptides that bind to a specific chemokine, CXCL8, using a mirror-image phage display method, which could help treat inflammation-related diseases.

Contribution

The study introduces the use of mirror-image phage display to identify proteolytically stable all-D-peptides with submicromolar affinity for CXCL8.

Findings

All-D-peptides with submicromolar affinity to CXCL8 were identified using mirror-image phage display.

These peptides disrupted CXCL8 dimerization and GAG binding without affecting cell migration.

The peptides showed structural diversity and selectivity for CXCL8 over related chemokines.

Abstract

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.

Figures