Inhibiting S100B(ββ) for Activating Wild-Type p53: Design of Stapled Peptides

Inhibiting S100B(ββ) for Activating Wild-Type p53: Design of Stapled Peptides
Title:
Inhibiting S100B(ββ) for Activating Wild-Type p53: Design of Stapled Peptides
Other Titles:
ACS Omega
Keywords:
Publication Date:
14 March 2019
Citation:
ACS Omega 2019, 4, 3, 5335-5344
Abstract:
S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetramerization and protein kinase C-dependent phosphorylation, consequently decreasing p53 DNA binding and transcriptional activity, and preventing apoptosis. Thus, S100B(ββ) is being pursued as a target for therapeutic inhibition. However, development of small molecule inhibitors targeting p53-interactions has met with limited success. In this work, we present a set of designed stapled peptide inhibitors of S100B(ββ), guided by the structure of the C-terminal domain of p53 complexed with S100B(ββ). We further modified a tightly binding stapled peptide with imaging agents and propose these as potential diagnostic agents to detect S100B(ββ) as a biomarker.
License type:
PublisherCopyrights
Funding Info:
Description:
The full paper is available for download at the publisher's URL here: https://doi.org/10.1021/acsomega.9b00097
ISSN:
2470-1343
Files uploaded:
File Size Format Action
There are no attached files.