title: Rational design of conformationally constrained cyclopentapeptide antagonists for C-x-C chemokine receptor 4 (CXCR4).
abstract: In the absence of an experimentally determined binding mode for the cyclopentapeptide CXCR4 antagonists, we have rationally designed conformationally constrained analogues to further probe the small peptide binding pocket of CXCR4. Two different rigidification strategies were employed, both resulting in highly potent ligands (9 and 13). The information provided by this cyclopentapeptide ligand series will be very valuable in the development of novel peptidomimetic CXCR4 antagonists.
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Breivika, NO-9037 Tromsø, Norway.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Mungalpara
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thiele
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Eriksen
authors.forename: Johann
authors.initials: J
authors.lastname: Eksteen
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
authors.forename: Jon
authors.initials: J
authors.lastname: Våbenø
mesh_terms: D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D057786:Peptidomimetics; D011487:Protein Conformation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D019718:Receptors, CXCR4; C577964:cyclo(4-amino-1-carbamimidoylpiperidine-4-carboxylic acid-arginyl-3-(2-naphthyl)alanyl-glycyl-tyrosyl)