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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Liu Y,Garnham CP,Roll-Mecak A,Tanner MEdoi
10.1016/j.bmcl.2013.05.069subject
Has Abstractpub_date
2013-08-01 00:00:00pages
4408-12issue
15eissn
0960-894Xissn
1464-3405pii
S0960-894X(13)00664-1journal_volume
23pub_type
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