Modulation of the Interaction between a Peptide Ligand and a G Protein-Coupled Receptor by Halogen Atoms.
Systematic halogenation of two native opioid peptides has shown that halogen atoms can modulate peptide-receptor interactions in different manners. First, halogens may produce a steric hindrance that reduces the binding of the peptide to the receptor. Second, chlorine, bromine, or iodine may improve peptide binding if their positive σ-hole forms a halogen bond interaction with negatively charged atoms of the protein. Lastly, the negative electrostatic potential of fluorine can interact with positively charged atoms of the protein to improve peptide binding.
Institut de Química Avançada de Catalunya (I.Q.A.C.-C.S.I.C.) , E-08034 Barcelona, Spain.
Mònica
M
Rosa
Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona , E-08193 Bellaterra, Barcelona, Spain.
Gianluigi
G
Caltabiano
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca , 37008 Salamanca, Spain ; Institute of Biomedical Research of Salamanca (IBSAL) , E-37007 Salamanca, Spain.
Katy
K
Barreto-Valer
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca , 37008 Salamanca, Spain ; Institute of Biomedical Research of Salamanca (IBSAL) , E-37007 Salamanca, Spain.
Verónica
V
Gonzalez-Nunez
Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona , E-08193 Bellaterra, Barcelona, Spain.
José C
JC
Gómez-Tamayo
CIC bioGUNE, Bizkaia Technological Park , 48160 Derio, Spain ; Ikerbasque, Basque Foundation for Science , E-48013 Bilbao, Spain.
Ana
A
Ardá
CIC bioGUNE, Bizkaia Technological Park , 48160 Derio, Spain ; Ikerbasque, Basque Foundation for Science , E-48013 Bilbao, Spain.
Jesús
J
Jiménez-Barbero
Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona , E-08193 Bellaterra, Barcelona, Spain.
Leonardo
L
Pardo
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Instituto de Neurociencias de Castilla y León (INCyL), University of Salamanca , 37008 Salamanca, Spain ; Institute of Biomedical Research of Salamanca (IBSAL) , E-37007 Salamanca, Spain.
Raquel E
RE
Rodríguez
Institut de Química Avançada de Catalunya (I.Q.A.C.-C.S.I.C.) , E-08034 Barcelona, Spain.
Gemma
G
Arsequell
Institut de Química Avançada de Catalunya (I.Q.A.C.-C.S.I.C.) , E-08034 Barcelona, Spain.
Gregorio
G
Valencia
G protein-coupled receptors; Halogen bond; Leu-enkephalin; drug design; endomorphin-1; halogenated peptides; neuropeptides; opioid receptors