Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0081068
Title: Inhibition of Nutlin-resistant HDM2 mutants by stapled peptides
Authors: Wei, S.J.
Joseph, T.
Chee, S.
Li, L.
Yurlova, L.
Zolghadr, K.
Brown, C.
Lane, D.
Verma, C. 
Ghadessy, F.
Issue Date: 20-Nov-2013
Citation: Wei, S.J., Joseph, T., Chee, S., Li, L., Yurlova, L., Zolghadr, K., Brown, C., Lane, D., Verma, C., Ghadessy, F. (2013-11-20). Inhibition of Nutlin-resistant HDM2 mutants by stapled peptides. PLoS ONE 8 (11) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0081068
Abstract: Pharmacological modulation of p53 activity is an attractive therapeutic strategy in cancers with wild-type p53. Presently in clinical trials, the small molecule Nutlin-3A competitively binds to HDM2, a key negative regulator of p53 and blocks its activity. We have described resistance mutations in HDM2 that selectively reduce affinity for Nutlin but not p53. In the present communication, we show that stapled peptides targeting the same region of HDM2 as Nutlin are refractory to these mutations, and display reduced discrimination between the wild-type and mutant HDM2s with regards to functional abrogation of interaction with p53. The larger interaction footprint afforded by stapled peptides suggests that this class of ligands may prove comparatively more resilient to acquired resistance in a clinical setting. © 2013 Jia Wei et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/100932
ISSN: 19326203
DOI: 10.1371/journal.pone.0081068
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