Phosphinic acid-based inhibitors of tubulin polyglutamylases.

Abstract:

:Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 μM) and the most potent inhibitor displayed an IC₅₀ value of 150 μM. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors.

journal_name

Bioorg Med Chem Lett

authors

Liu Y,Garnham CP,Roll-Mecak A,Tanner ME

doi

10.1016/j.bmcl.2013.05.069

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

4408-12

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00664-1

journal_volume

23

pub_type

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