title: The first dipeptide ligand of translocator protein: Design and anxiolytic activity.
abstract: On the basis of the structure of Alpidem, a pyrazolopyrimidine ligand of the translocator protein (TSPO), a dipeptide TSPO ligand, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), was designed and synthesized using our own original peptide design strategy. This compound exhibited anxiolytic activity in BALB/cAnN mice in the "open-field" test and in outbred CD1 mice in the "elevated plus maze" test. The stereoselectivity of the anxiolytic effect of GD-23 is demonstrated. The results of this study suggest that GD-23 is a ligand of the translocator protein, and its structure can become the basis for creating anxiolytics with a fundamentally new mechanism of action.
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia. tata-sosnovka@mail.ru.
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Deeva
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
authors.forename: G V
authors.initials: GV
authors.lastname: Mokrov
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
authors.forename: S A
authors.initials: SA
authors.lastname: Yarkov
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Yarkova
authors.affiliation: Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; C463819:Bzrp protein, mouse; D002491:Central Nervous System Agents; D004151:Dipeptides; D007546:Isoquinolines; D008024:Ligands; C000609774:N-carbobenzoxy-tryptophyl-isoleucine amide; D018079:Receptors, GABA; C037850:PK 11195