Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbβ₃

Andrei A Krysko; Georgiy V Samoylenko; Pavel G Polishchuk; Marina S Fonari; Victor Ch Kravtsov; Sergei A Andronati; Tatyana A Kabanova; Janusz Lipkowski; Tetiana M Khristova; Victor E Kuz'min; Vladimir M Kabanov; Olga L Krysko; Alexandre A Varnek

doi:10.1016/j.bmc.2013.05.019

Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbβ₃

Bioorg Med Chem. 2013 Aug 1;21(15):4646-61. doi: 10.1016/j.bmc.2013.05.019. Epub 2013 May 22.

Authors

Andrei A Krysko¹, Georgiy V Samoylenko, Pavel G Polishchuk, Marina S Fonari, Victor Ch Kravtsov, Sergei A Andronati, Tatyana A Kabanova, Janusz Lipkowski, Tetiana M Khristova, Victor E Kuz'min, Vladimir M Kabanov, Olga L Krysko, Alexandre A Varnek

Affiliation

¹ A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lustdorfskaya Doroga 86, Odessa 65080, Ukraine. peptides@paco.net

PMID: 23757209
DOI: 10.1016/j.bmc.2013.05.019

Abstract

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born's method was shown to be due to inhibition of fibrinogen binding to αIIbβ₃. Molecular docking of RGD mimetics to αIIbβ₃ receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Biomimetic Materials / chemistry*
Biomimetic Materials / metabolism
Biomimetic Materials / pharmacology
Crystallography, X-Ray
Fibrinogen / antagonists & inhibitors
Fibrinogen / metabolism
Humans
Isoindoles / chemistry*
Isoindoles / metabolism
Isoindoles / pharmacology
Ligands
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Oligopeptides / chemistry*
Oligopeptides / metabolism
Oligopeptides / pharmacology
Phthalimides / chemistry*
Phthalimides / metabolism
Phthalimides / pharmacology
Platelet Aggregation / drug effects
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
Protein Binding

Substances

Isoindol-1-one
Isoindoles
Ligands
Oligopeptides
Phthalimides
Platelet Glycoprotein GPIIb-IIIa Complex
phthalimidine
arginyl-glycyl-aspartic acid
Fibrinogen