Hitting a moving target: targeting transient protein states

Matthias R Bauer; Frank M Boeckler

doi:10.1016/j.str.2013.11.003

Hitting a moving target: targeting transient protein states

Structure. 2013 Dec 3;21(12):2095-7. doi: 10.1016/j.str.2013.11.003.

Authors

Matthias R Bauer¹, Frank M Boeckler

Affiliation

¹ Laboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.

PMID: 24315455
DOI: 10.1016/j.str.2013.11.003

Abstract

In this issue of Structure, Bista and colleagues report that inhibitors of the MDM2/p53 interaction can be designed to interact with a transiently folded α-helical segment of the MDM2 lid region. This suggests that targeting transient protein states in PPI inhibitor design could be a promising strategy to improve affinity and/or selectivity profiles.

Publication types

Comment

MeSH terms

Dipeptides / chemistry*
Humans
Hydroxamic Acids / chemistry*
Proto-Oncogene Proteins c-mdm2 / chemistry*
Tryptophan / analogs & derivatives*
Tryptophan / chemistry
Tumor Suppressor Protein p53 / chemistry*

Substances

Dipeptides
Hydroxamic Acids
KK271 compound
Tumor Suppressor Protein p53
YH300 compound
Tryptophan
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2