Ligand-Based NMR Study of C-X-C Chemokine Receptor Type 4 (CXCR4)-Ligand Interactions on Living Cancer Cells.

Abstract	Peptide-binding G protein-coupled receptors (GPCRs) are key effectors in numerous pathological and physiological pathways. The assessment of the receptor-bound conformation of a peptidic ligand within a membrane receptor such as a GPCR is of great impact for a rational drug design of more potent analogues. In this work, we applied multiple ligand-based nuclear magnetic resonance (NMR) methods to study the interaction of peptide heptamers, derived from the C-X-C Motif Chemokine 12 (CXCL12), and the C-X-C Chemokine Receptor Type 4 (CXCR4) on membranes of human T-Leukemia cells (CCRF-CEM cells). This study represents the first structural investigation reporting the receptor-bound conformation of a peptide to a GPCR directly on a living cell. The results obtained in the field of CXCL12/CXCR4 are proofs of concept, although important information for researchers dealing with the CXCR4 field arises. General application of the presented NMR methodologies is possible and surely may help to boost the development of new therapeutic agents targeting GPCRs.
Authors	Diego Brancaccio, Donatella Diana, Salvatore Di Maro, Francesco Saverio Di Leva, Stefano Tomassi, Roberto Fattorusso, Luigi Russo, Stefania Scala, Anna Maria Trotta, Luigi Portella, Ettore Novellino, Luciana Marinelli, Alfonso Carotenuto
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 61 Issue 7 Pg. 2910-2923 (04 12 2018) ISSN: 1520-4804 [Electronic] United States
PMID	29522685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CXCL12 protein, human CXCR4 protein, human Chemokine CXCL12 Receptors, CXCR4 Receptors, G-Protein-Coupled Guanidine
Topics	Animals Cell Line Cell Line, Tumor Cell Survival Chemokine CXCL12 (antagonists & inhibitors, metabolism) Cricetinae Cricetulus Epitope Mapping Guanidine (metabolism) Humans Leukemia, T-Cell (metabolism) Magnetic Resonance Spectroscopy Models, Molecular Molecular Conformation Molecular Dynamics Simulation Neoplasms (metabolism) Receptors, CXCR4 (antagonists & inhibitors, metabolism) Receptors, G-Protein-Coupled (metabolism)

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