Peptides targeting chemokine receptor CXCR4: Structural behavior and biological binding studies

Susan Costantini, Raffaele Raucci, Giovanni Colonna, Flavia Anna Mercurio, Anna Maria Trotta, Ringhieri Paola, Marilisa Leone, Filomena Rossi, Carmela Pellegrino, Giuseppe Castello, Stefania Scala

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)270-278
Number of pages9
JournalJournal of Peptide Science
Issue number4
Publication statusPublished - 2014


  • antagonists
  • cancer
  • CXC chemokines
  • CXCR4
  • inflammation
  • molecular docking
  • molecular dynamics
  • molecular recognition
  • NMR

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Structural Biology


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