Design, synthesis, and biological evaluation of scaffold-based tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)

Research output: Contribution to journalJournal articlepeer-review

  • Zack G Zachariassen
  • Stefanie Thiele
  • Erik A Berg
  • Pernille Rasmussen
  • Torgils Fossen
  • Rosenkilde, Mette
  • Jon Våbenø
  • Bengt Erik Haug

Structure-activity relationship studies of the cyclopentapeptide CXCR4 antagonists (cyclo(-l-/d-Arg(1)-Arg(2)-2-Nal(3)-Gly(4)-d-Tyr(5)-)) suggest that the l-/d-Arg(1)-Arg(2)-2-Nal(3) tripeptide sequence contained within these cyclopentapeptides serves as a recognition motif for peptidic CXCR4 antagonists. Starting by dissecting the cyclopentapeptide structure and reintroducing cyclic constraints in a stepwise manner, we here report a novel class of scaffold-based tripeptidomimetic CXCR4 antagonists based on the d-Arg-Arg-2-Nal motif. Biological testing of the prototype compounds showed that they represent new peptidomimetic hits; importantly, the modular nature of the scaffold provides an interesting starting point for future ligand optimization.

Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Issue number17
Pages (from-to)4759-69
Number of pages11
Publication statusPublished - 1 Sep 2014

    Research areas

  • Dose-Response Relationship, Drug, Drug Design, Humans, Molecular Conformation, Peptides, Cyclic, Receptors, CXCR4, Structure-Activity Relationship

ID: 137371407