TY - JOUR
T1 - Ligand-Based NMR Study of C-X-C Chemokine Receptor Type 4 (CXCR4)-Ligand Interactions on Living Cancer Cells
AU - Brancaccio, Diego
AU - Diana, Donatella
AU - Di Maro, Salvatore
AU - Di Leva, Francesco Saverio
AU - Tomassi, Stefano
AU - Fattorusso, Roberto
AU - Scala, Stefania
AU - Trotta, Anna Maria
AU - Portella, Luigi
AU - Novellino, Ettore
AU - Marinelli, Luciana
AU - Carotenuto, Alfonso
PY - 2018/4/12
Y1 - 2018/4/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045584583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045584583&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.7b01830
DO - 10.1021/acs.jmedchem.7b01830
M3 - Article
AN - SCOPUS:85045584583
VL - 61
SP - 2910
EP - 2923
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 7
ER -