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.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.