Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles

Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles
Title:
Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles
Other Titles:
Chemical Science
Keywords:
Publication Date:
30 May 2019
Citation:
Yuen, T. Y., Brown, C. J., Xue, Y., Tan, Y. S., Ferrer Gago, F. J., Lee, X. E., Neo, J. Y., Thean, D., Kaan, H., Partridge, A. W., Verma, C. S., Lane, D. P., & Johannes, C. W. (2019). Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles. Chemical science, 10(26), 6457–6466. https://doi.org/10.1039/c9sc01456j
Abstract:
All-hydrocarbon, i, i+7 stapled peptide inhibitors of the p53-Mdm2 interaction have emerged as promising new leads for cancer therapy. Typical chemical synthesis via olefin metathesis results in the formation of both E- and Z-isomers, an observation that is rarely disclosed but may be of importance in targeting PPI. In this study, we evaluated the effect of staple geometry on the biological activity of five p53-reactivating peptides. We also present strategies for the modulation of the E/Z ratio and attainment of the hydrogenated adduct through repurposing of the metathesis catalyst.
License type:
http://creativecommons.org/licenses/by-nc/4.0/
Funding Info:
Funded by the A*STAR JCO Visiting Investigatorship Programme (JCO 1235d00048) and the Industry Alignment Fund (Pre-positioning, HBMS domain H17/01/a0/010).
Description:
ISSN:
2041-6520
2041-6539
Files uploaded:

File Size Format Action
1062-stereoisomerism-of-stapled-peptide.pdf 1.16 MB PDF Open