Methods for purifying proteins having a tubulin carboxypeptidase activity and peptidic based inhibitors thereof
AssigneesCentre National De La Recherche Scientifique, Universite De Montpellier
InventorsKrzysztof Rogowski, Siem Van Der Laan
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Abstract
The invention relates to a method for purifying proteins having a tubulin carboxypeptidase activity from a biological extract, comprising polymerization/depolymerization cycle performed on a biological extract in presence of microtubules. The invention further relates to a peptidic based inhibitor for use in the treatment of a disorder involving altered microtubule detyrosination in an animal, wherein the peptidic based inhibitor comprises a peptidic moiety constituted of 1 to 20 amino acids, said peptidic moiety having an amino acid selected from Y or F at the C-terminal position, and wherein the peptidic based inhibitor inhibits at least partially a tubulin carboxypeptidase activity.
Claims6
A method of treatment of a disorder involving altered microtubule detyrosination in a subject in need thereof comprising administering to the subject in need thereof an amino-acid or peptidic based inhibitor that inhibits, at least partially, a tubulin carboxypeptidase activity, wherein the amino acid or peptidic based inhibitor is selected from the group consisting of:
- a Tyr amino-acid (Y) modified with an epoxysuccinyl group, or a peptidic moiety consisting of an amino acid sequence selected from the group consisting of EDY, and EEY, where the tyrosine residue is chemically modified with an epoxysuccinyl group;
- a peptidic moiety of 2 to 19 amino acids of the most C-terminal amino acids of SEQ ID NO:12 where the C-terminal position is a tyrosine residue chemically modified with an epoxysuccinyl group;
- and
- a peptidic moiety consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO:13, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:17, and SEQ ID NO:
- 18, where the C-terminal position is a tyrosine residue chemically modified with an epoxysuccinyl group.
Dependencies are inferred from the claim text.