Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists.

Autor:	Neochoritis CG; Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands., Kazemi Miraki M; Chemistry Department, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran., Abdelraheem EMM; Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands., Surmiak E; Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland., Zarganes-Tzitzikas T; Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands., Łabuzek B; Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland., Holak TA; Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland., Dömling A; Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9700 AD Groningen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Beilstein journal of organic chemistry [Beilstein J Org Chem] 2019 Feb 20; Vol. 15, pp. 513-520. Date of Electronic Publication: 2019 Feb 20 (Print Publication: 2019).
DOI:	10.3762/bjoc.15.45
Abstrakt:	Macrocycles were designed to antagonize the protein-protein interaction p53-MDM2 based on the three-finger pharmacophore F 19 W 23 L 25 . The synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library for p53-MDM2 inhibition by fluorescence polarization and 1 H, 15 N HSQC NMR measurements confirm MDM2 binding.
Databáze:	MEDLINE
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