Towards More Drug-like Proteomimetics: Two-faced, Synthetic α-helix Mimetics Based on a Purine Scaffold

Overview

Journal Org Biomol Chem

Publisher Royal Society of Chemistry

Specialties Biochemistry
Chemistry

Date 2015 Jul 25

PMID 26204921

Citations 8

Authors

M E Lanning

P T Wilder

H Bailey

B Drennen

M Cavalier

L Chen

J L Yap

M Raje

S Fletcher

Affiliations

Soon will be listed here.

Abstract

Mimicry of two faces of an α-helix might yield more potent and more selective inhibitors of aberrant, helix-mediated protein-protein interactions (PPI). Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on opposing faces of the Bak-BH3 α-helix.

Citing Articles

Discovery of -sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors.

Chen L, Chauhan J, Yap J, Goodis C, Wilder P, Fletcher S RSC Med Chem. 2023; 14(1):103-112.

PMID: 36760746 PMC: 9890589. DOI: 10.1039/d2md00277a.

Scaffold hopping from indoles to indazoles yields dual MCL-1/BCL-2 inhibitors from MCL-1 selective leads.

Drennen B, Goodis C, Bowen N, Yu W, Vickers G, Wilder P RSC Med Chem. 2022; 13(8):963-969.

PMID: 36092148 PMC: 9384788. DOI: 10.1039/d2md00095d.

Recent applications of covalent chemistries in protein-protein interaction inhibitors.

Chan A, Goodis C, Pommier E, Fletcher S RSC Med Chem. 2022; 13(8):921-928.

PMID: 36092144 PMC: 9384789. DOI: 10.1039/d2md00112h.

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2.

Conlon I, Drennen B, Lanning M, Hughes S, Rothhaas R, Wilder P ChemMedChem. 2020; 15(18):1691-1698.

PMID: 32583936 PMC: 8477420. DOI: 10.1002/cmdc.202000278.

Targeting the Side-Chain Convergence of Hydrophobic α-Helical Hot Spots To Design Small-Molecule Mimetics: Key Binding Features for , + 3, and + 7.

Wang Z, Ji H J Med Chem. 2019; 62(21):9906-9917.

PMID: 31593458 PMC: 7872147. DOI: 10.1021/acs.jmedchem.9b01324.

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