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. 2008 Feb;3(2):230-2.
doi: 10.1002/cmdc.200700281.

A small molecular scaffold for selective inhibition of Wip1 phosphatase

Jeong Bang  1 , Hiroshi Yamaguchi, Stewart R Durell, Ettore Appella, Daniel H Appella
Affiliations

A small molecular scaffold for selective inhibition of Wip1 phosphatase

Jeong Bang et al. ChemMedChem. 2008 Feb.

Abstract

Using a pyrrole-based scaffold, we developed a series of small molecules that mimic the three-dimensional arrangement of the polar and hydrophobic functional groups of the best cyclic-peptide inhibitor. Iterative optimization cycles of design, synthesis and kinetic testing has lead to an effective inhibitor of Wip1, that is selective for this phosphatase over others. The picture shows the structure of the best inhibitor bound to the active site of the enzyme.

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Figures

Figure 1
Figure 1
(A) Chemical structure of c(MpSIpYVA), (B) pyrrole scaffold to mimic the cyclic peptide (sidechain mimics labeled in parentheses).
Figure 2
Figure 2
Comparison of Bound Cyclic peptide (A) with Entry 9 (B).
Figure 3
Figure 3
Model of Pyrrole 9 bound to Wip1. Residues K238, D264, and F268 are unique to Wip1.
Scheme 1
Scheme 1
See this image and copyright information in PMC

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