Conotoxin peptides

Details Conotoxin peptides Conotoxin peptides

C - Chemistry, Metallurgy

12

N

C12N 15/12 (2006.01) C07K 14/435 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2216751

The present invention is directed to conotoxin peptides, specifically .delta.- conotoxin PVIA and µ-conotoxin PIIIA. .delta.-conotoxin PVIA is found in the Eastern Pacific fish hunting species of cone snails Conus purpurascens. It consists of 29 amino acid residues of the sequence: Glu-Ala-Cys-Tyr-Ala-Xaa1- Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa2-Gly-Leu-Cys-Cys-Ser-Glu-Phe-Cys-Leu-Pro-Gly- Val-Cys-Pro-Gly (SEQ ID NO:1) where Xaa1 or Xaa2 is Pro or 4-trans- hydroxyproline. The C-terminus may be free or amidated. .delta.-conotoxin PVIA is vertebrate specific and targets voltage-sensitive Na+ channels. µ- conotoxin PIIIA is also found in Conus purpurascens. It consists of 22 amino acid residues of the sequence: Xaa1-Arg-Leu-Cys-Cys-Gly-Phe-Xaa2-Lys-Ser-Cys- Arg-Ser-Arg-Gln-Cys-Lys-Xaa2-His-Arg-Cys-Cys (SEQ ID NO:2) where Xaa1 represents pyroglutamate or glutamine and Xaa2 represents 4-trans- hydroxyproline or proline. This latter peptide targets sodium channels.

Peptides de conotoxine, en particulier de .delta.-conotoxine PVIA et de µ-conotoxine PIIIA. La .delta.-conotoxine PVIA se trouve dans une espèce de mollusque conidé vivant dans le Pacifique est, chassant le poisson, appelée Conus purpurascens. Cette substance est composée de 29 restes d'acides aminés de la séquence Glu-Ala-Cys-Tyr-Ala-Xaa¿1?-Gly-Thr-Phe-Cys-Gly-Ile-Lys-Xaa¿2?-Gly-Leu-Cys-Cys-Ser-Glu-Phe-Cys-Leu-Pro-Gly-Val-Cys-Pro-Gly (SEQ ID No. 1), où Xaa¿1? ou Xaa¿2? sont Pro ou 4-trans-hydroxyproline. La terminaison C peut être libre ou munie d'un amide. La .delta.-conotoxine PVIA est spécifique aux vertégrés et cible des canaux Na?+¿ sensibles à la tension. La µ-conotoxine PIIIA se trouve également dans le Conus purpurascens. Elle consiste en 22 restes d'acides aminés de la séquence Xaa¿1?-Arg-Leu-Cys-Cys-Gly-Phe-Xaa¿2?-Lys-Ser-Cys-Arg-Ser-Arg-Gln-Cys-Lys-Xaa¿2?-His-Arg-Cys-Cys (SEQ ID No. 2) où Xaa¿1? représente pyroglutamate ou glutamine et Xaa¿2? représente 4-trans-hydroxyproline ou proline. Ce dernier peptide cible les canaux de sodium.

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