Journal article
Exploiting the Biginelli reaction: Nitrogen-rich pyrimidine-based tercyclic α-helix mimetics
Z Lim, PJ Duggan, SS Wan, G Lessene, AG Meyer, KL Tuck
Tetrahedron | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2016
Abstract
Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an α-helix and also possess improved aqueous solubility were prepared. A Biginelli-oxidation process was used to form the central pyrimidine ring of these scaffolds, which was subsequently manipulated to form pyrimidine-based tercyclic α-helix mimetics. A pyrimidine-based scaffold designed to mimic the α-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the Bcl-xL/Bak protein-protein interaction. The pyrimidine-based tercyclic α-helix mimetics, and the putative Bcl-xL inhibitor, were assessed using a luminescence com..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
The authors acknowledge the support of the School of Chemistry, Monash University, and CSIRO Manufacturing; Biomedical Manufacturing Program. Z.L. gratefully acknowledges receipt of a Faculty of Science Dean's Postgraduate Research Scholarship and a top-up scholarship from CSIRO. We are also thankful to Dr. Craig Forsyth for X-ray crystal structure determination and the Victorian Partnership for Advanced Computing for access to their facilities for the molecular modelling component of this research. Part of this work was supported by an NHMRC (GNT1025138), the WEHI de Burgh Fellowship to GL, the Australian Cancer Research Foundation. Part of this work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (#361646).