title: Agonists for the Chemokine Receptor CXCR4.
abstract: The development of agonists for the chemokine receptor CXCR4 could provide promising therapeutic candidates. On the basis of previously forwarded two site model of chemokine-receptor interactions, we hypothesized that linking the agonistic N-terminus of SDF-1 to the T140 backbone would yield new high-affinity agonists of CXCR4. We developed chimeras with the agonistic SDF-1 N-terminus grafted to a T140 side chain and tested their binding affinity and chemotactic agonist activity. While chimeras with the peptide grafted onto position 12 of T140 remained high-affinity antagonists, those bearing the peptide on position 14 were in part agonists. One chimera was a full CXCR4 agonist with 25 nM affinity, and several chimeras showed low nanomolar affinities with partial agonist activity. Our results confirmed that we have developed high-affinity agonists of CXCR4.
authors.forename: Marilou
authors.initials: M
authors.lastname: Lefrançois
authors.forename: Marie-Reine
authors.initials: MR
authors.lastname: Lefebvre
authors.forename: Geneviève
authors.initials: G
authors.lastname: Saint-Onge
authors.forename: Philip E
authors.initials: PE
authors.lastname: Boulais
authors.forename: Simon
authors.initials: S
authors.lastname: Lamothe
authors.forename: Richard
authors.initials: R
authors.lastname: Leduc
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavigne
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Heveker
authors.forename: Emanuel
authors.initials: E
authors.lastname: Escher