title: Synthesis and allosteric modulation of the dopamine receptor by peptide analogs of L-prolyl-L-leucyl-glycinamide (PLG) modified in the L-proline or L-proline and L-leucine scaffolds.
abstract: Novel analogs of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other amino acids based on a 3,5-disubstituted proline scaffold. In some examples, the L-leucyl residue was also replaced by L-valine. These analogs were tested for their ability to enhance the binding of [(3)H]-N-propylnorapomorphine to short isoform of human dopamine D₂ receptors. Compounds 18b and 19b, increased [(3)H] NPA binding at concentrations between 10(-12) and 10(-9) M, which is similar to the effect of PLG in this assay and, provides evidences that these compounds are acting as allosteric modulators of dopamine D₂ receptors.
authors.affiliation: Departamento de Química Orgánica, Facultade de Farmacia, Campus Vida s/n, Universidade de Santiago de Compostela, E-15782, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Ferreira da Costa
authors.forename: Olga
authors.initials: O
authors.lastname: Caamaño
authors.forename: Franco
authors.initials: F
authors.lastname: Fernández
authors.forename: Xerardo
authors.initials: X
authors.lastname: García-Mera
authors.forename: Ivo E
authors.initials: IE
authors.lastname: Sampaio-Dias
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Brea
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Cadavid
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D017448:Receptors, Dopamine D2; D011392:Proline; D007930:Leucine
keywords: Dopamine receptors; PLG; Peptide mimetics