Proteomimetic libraries: design, synthesis, and evaluation of p53-MDM2 interaction inhibitors

Cited 71 time in scopus
Metadata Downloads
Title
Proteomimetic libraries: design, synthesis, and evaluation of p53-MDM2 interaction inhibitors
Author(s)
F Lu; Seung-Wook ChiDo-heyoung Kim; Kyou Hoon Han; I D Kuntz; R K Guy
Bibliographic Citation
Journal of Combinatorial Chemistry, vol. 8, no. 3, pp. 315-325
Publication Year
2006
Abstract
The p53-MDM2 interaction regulates p53-mediated cellular responses to DNA damage, and MDM2 is overexpressed in 7% of all cancers. Structure-based computational design was applied to this system to design libraries centered on a scaffold that projects side chain functionalities with distance and angular relationships equivalent to those seen in the MDM2 interacting motif of p53. A library of 173 such compounds was synthesized using solution phase parallel chemistry. The in vitro competitive ability of the compounds to block p53 peptide binding to MDM2 was determined using a fluorescence polarization competition assay. The most active compound bound with Kd = 12 μM, and its binding was characterized by 15N-1H HSQC NMR.
ISSN
1520-4766
Publisher
American Chemical Society
DOI
http://dx.doi.org/10.1021/cc050142v
Type
Article
Appears in Collections:
Division of Biomedical Research > 1. Journal Articles
Division of Bio Technology Innovation > Core Research Facility & Analysis Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.