title: Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis.
abstract: Conformation of bicyclic guanidines with kappa-opioid receptor activity derived in our laboratory from a positional scanning synthetic combinatorial library is presented in this work. We propose a common bioactive conformation and putative pharmacophoric features by means of 3D similarity methods. Our 'Y' shape molecular binding model explains structure-activity relationships and suggests that the guanidine functionality and a 4-methoxybenzyl group may be involved in key interactions with the receptor. Comparison of our model with known opiates suggest a similar binding mode showing that the bicyclic guanidines presented in this work are suitable scaffolds for further development of new opioid receptors ligands.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 5775 Old Dixie Highway, Fort Pierce, FL 34946, USA. kmartinez@tpims.org
authors.forename: Karina
authors.initials: K
authors.lastname: Martínez-Mayorga
authors.forename: Jose L
authors.initials: JL
authors.lastname: Medina-Franco
authors.forename: Marc A
authors.initials: MA
authors.lastname: Giulianotti
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Colette T
authors.initials: CT
authors.lastname: Dooley
authors.forename: Jon R
authors.initials: JR
authors.lastname: Appel
authors.forename: Richard A
authors.initials: RA
authors.lastname: Houghten
mesh_terms: D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D019295:Computational Biology; D019791:Guanidine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011957:Receptors, Opioid / Q000737:chemistry* / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D019791:Guanidine