title: Biotin ergopeptide probes for dopamine receptors.
abstract: The incorporation of chemical modifications into the structure of bioactive compounds is often difficult because the biological properties of the new molecules must be retained with respect to the native ligand. Ergopeptides, with their high affinities at D(1) and D(2) dopamine receptors, are particularly complex examples. Here, we report the systematic derivatization of two ergopeptides with different peptide-based spacers and their evaluation by radioligand binding assays. Selected spacer-containing ergopeptides with minimal biological alteration and a proper anchoring point were further derivatized with a biotin reporter. Detailed characterization studies identified 13 as a biotin ergopeptide maintaining high affinity and agonist behavior at dopamine receptors, being a useful tool for the study of heteromers involving D(1)R, D(2)R, or D(3)R.
authors.affiliation: Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Vendrell
authors.forename: Anabel
authors.initials: A
authors.lastname: Molero
authors.forename: Sergio
authors.initials: S
authors.lastname: González
authors.forename: Kamil
authors.initials: K
authors.lastname: Pérez-Capote
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Antoni
authors.initials: A
authors.lastname: Cortés
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004879:Ergotamines / Q000138:chemical synthesis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D017447:Receptors, Dopamine D1 / Q000302:isolation & purification / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D004879:Ergotamines; D019151:Peptide Library; D010455:Peptides; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001710:Biotin