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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.

SUBMITTER: Lefrancois M

PROVIDER: S-EPMC3155278 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Agonists for the Chemokine Receptor CXCR4.

Lefrançois Marilou M Lefebvre Marie-Reine MR Saint-Onge Geneviève G Boulais Philip E PE Lamothe Simon S Leduc Richard R Lavigne Pierre P Heveker Nikolaus N Escher Emanuel E

ACS medicinal chemistry letters 20110606 8

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 ...[more]

PMID: 21841963

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