title: Progress toward rationally designed small-molecule peptide and peptidomimetic CXCR4 antagonists.
abstract: Over the last 5 years, X-ray structures of CXCR4 in complex with three different ligands (the small-molecule antagonist IT1t, the polypeptide antagonist CVX15 and the viral chemokine antagonist vMIP-II) have been released. In addition to the inherent scientific value of these specific X-ray structures, they provide a reliable structural foundation for studies of the molecular interactions between CXCR4 and its key peptide ligands (CXCL12 and HIV-1 gp120), and serve as valuable templates for further development of small-molecule CXCR4 antagonists with therapeutic potential. We here review recent computational studies of the molecular interactions between CXCR4 and its peptide ligands - based on the X-ray structures of CXCR4 - and the current status of small-molecule peptide and peptidomimetic CXCR4 antagonists.
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Breivika, NO-9037 Tromsø, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Våbenø
authors.affiliation: Department of Chemistry & Centre for Pharmacy, University of Bergen, Allégaten 41, NO-5007 Bergen, Norway.
authors.forename: Bengt Erik
authors.initials: BE
authors.lastname: Haug
authors.affiliation: Laboratory for Molecular Pharmacology, Department of Neuroscience & Pharmacology, Faculty of Health & Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D010455:Peptides; D057786:Peptidomimetics; D019718:Receptors, CXCR4; D054852:Small Molecule Libraries