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Peptides targeting chemokine receptor CXCR4: structural behavior and biological binding studies†
Article first published online: 28 JAN 2014
Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 20, Issue 4, pages 270–278, April 2014
How to Cite
Costantini, S., Raucci, R., Colonna, G., Mercurio, F. A., Trotta, A. M., Paola, R., Leone, M., Rossi, F., Pellegrino, C., Castello, G. and Scala, S. (2014), Peptides targeting chemokine receptor CXCR4: structural behavior and biological binding studies. J. Peptide Sci., 20: 270–278. doi: 10.1002/psc.2614
- Issue published online: 12 MAR 2014
- Article first published online: 28 JAN 2014
- Manuscript Revised: 20 DEC 2013
- Manuscript Accepted: 20 DEC 2013
- Manuscript Received: 19 OCT 2013
- CXC chemokines;
- molecular dynamics;
- molecular docking;
- molecular recognition
CXCR4 is a G-protein-coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems. CXCL12/CXCR4 axis plays a central role in diseases, such as HIV, cancer, WHIM syndrome, rheumatoid arthritis, pulmonary fibrosis, and lupus and, hence, indicated as putative therapeutic target. Although multiple CXCR4 antagonists have been developed, there is only one marketed drug, plerixafor, indicated for stem cell mobilization in poor mobilizer patients. In this work, we have designed and synthesized two peptides, six and seven residues long, using as template the N-terminal region of CXCL12; analyzed their conformations by CD, NMR, and molecular dynamics simulations; simulated their complexes with CXCR4 by docking methods; and validated these data by in vitro studies. The results showed that the two peptides are rather flexible in aqueous solution lacking ordered secondary structure elements and present a promising affinity for CXCR4. This affinity is not revealed for CXCR7, indicating a specificity for CXCR4. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.