Towards more drug-like proteomimetics: two-faced, synthetic α-helix mimetics based on a purine scaffoldElectronic supplementary information (ESI) available: Synthetic procedures and fluorescence anisotropy competition assays. See DOI: 10.1039/c5ob00478k

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...

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Main Authors: Lanning, M. E, Wilder, P. T, Bailey, H, Drennen, B, Cavalier, M, Chen, L, Yap, J. L, Raje, M, Fletcher, S
Format: Article
Language:English
Online Access:Get full text
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Summary: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. Key residues on opposing faces of the Bak-BH3 α-helix were recapitulated by the 2,6,9-tri-substitution of a purine scaffold.
ISSN:1477-0520
1477-0539
DOI:10.1039/c5ob00478k