title: [The study of biologically active conformation of cholecystokinin-4 dipeptide analog GB-115].
abstract: The conformational analysis with 1H NMR spectroscopy method in solution and the structure-activity relationship study of a series sterically restricted analogs allowed to detect the possible biologically active conformation of N-(6-phenylhexanoyl)glycyl-tryptophan amide (GB-115), a highly active dipeptide cholecystokinin-4 analog with anxiolytic activity. The structure-activity relationship study of GB-115 and the series of its' glycine- and proline-containing analogs with different C-terminal substitute detected the anxiolytic activity of compounds with beta-turn like conformation and inactivity of compounds with gamma-turn like conformation. So, the GB-115 biologically active conformation is beta-turn. The results of nuclear Overhauser effect study permitted to qualify the betaII-turn conformation as GB-115 biologically active conformation. The following synthesis of sterically restricted GB-115 analogs (2S)-2-{(3R)-3-[(6-phenylhexanoyl)amino]-2-oxopyrrolidin-1-yl}-3-(1H-indol-3-yl)propionic acid ethyl ester, N-(6-phenylhexanoyl)glycyl-N(alpha)(methyl)-tryptophan ethyl ester, (2S)-2-[10,11-dihydro-5H-dibenzo[b,f] azepin-5-carbonyl)-amino]-3-(1H-indol-3-yl)propionic acid methyl ester and (2S)-2-[({3-[(ethoxycarbonyl)amino]-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl}carbonyl)amino]-3-(1H-indol-3-yl)propionic acid methyl ester confirmed the estimated type of GB-115 biologically active conformation.
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.forename: V P
authors.initials: VP
authors.lastname: Lezina
authors.forename: E P
authors.initials: EP
authors.lastname: Kir'ianova
authors.forename: O A
authors.initials: OA
authors.lastname: Deeva
authors.forename: L G
authors.initials: LG
authors.lastname: Kolik
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000473:pathology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary; D051381:Rats; D013329:Structure-Activity Relationship; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D014364:Tryptophan / Q000737:chemistry
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; C520797:GB-115; D013758:Tetragastrin; D014364:Tryptophan; D011392:Proline; D005998:Glycine