title: RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor.
abstract: The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)β(3) integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments.
authors.affiliation: A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lustdorfskaya doroga 86, Odessa 65080, Ukraine. peptides@paco.net
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Krysko
authors.forename: Georgiy V
authors.initials: GV
authors.lastname: Samoylenko
authors.forename: Pavel G
authors.initials: PG
authors.lastname: Polishchuk
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Andronati
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Kabanova
authors.forename: Tetiana M
authors.initials: TM
authors.lastname: Khristova
authors.forename: Victor E
authors.initials: VE
authors.lastname: Kuz'min
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Kabanov
authors.forename: Olga L
authors.initials: OL
authors.lastname: Krysko
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Varnek
authors.forename: Ruslan Ya
authors.initials: RY
authors.lastname: Grygorash
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005340:Fibrinogen / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010797:Phthalimides / Q000138:chemical synthesis*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D039341:Receptors, Fibrinogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012984:Software; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D007546:Isoquinolines; D008024:Ligands; D009842:Oligopeptides; D010797:Phthalimides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D039341:Receptors, Fibrinogen; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D001120:Arginine; D000077466:Tirofiban; D016650:Fluorescein-5-isothiocyanate; C039109:isoquinoline