Conus-based toxin peptides, nucleic acids encoding same and uses thereof in modulating NMDA receptors
AssigneeTechnion Research & Development Foundation Limited
InventorsShai Berlin, Ido Carmi, Shaden Zoabi
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Abstract
Provided herein are modified forms of Conantokin peptides, including, modified Con-P peptides, nucleic acids encoding the same and compositions thereof. Further provided are nucleic acid molecules encoding for chimeric modified conantokin polypeptides to be expressed in or on a membrane of a target cells, compositions comprising the same and uses thereof for treating various neurodegenerative conditions.
Claims16
A modified conantokin-P (con-P) peptide comprising at least one amino acid residue substitution as compared to a naturally occurring native conantokin-P peptide, wherein the amino acid substitution comprises substitution of at least one gamma carboxyglutamate acid residue of the naturally occurring conantokin-P with at least one amino acid selected from the group consisting Aspartate, Alanine and Glycine, wherein the modified con-P peptide comprises the amino acid sequence as denoted by any one of SEQ ID NOs:
- 5-7.
A nucleic acid molecule for expressing a chimeric modified conantokin polypeptide in or on a membrane of a target cell, the nucleic acid molecule comprising:
- a first nucleotide sequence encoding for a modified conantokin peptide, wherein the modified conantokin peptide is a modified conan tokin-P (con-P) peptide comprising the amino acid sequence as denoted by any one of SEQ ID NOs:
- 5-7;
- a second nucleotide sequence encoding for a transmembrane domain, capable of directing the expressed modified conantokin peptide to the membrane;
- and
- a third nucleotide sequence, being a regulatory sequence capable of affecting expression of the modified conantokin peptide within the target cell.
A chimeric polypeptide comprising a modified conantokin peptide domain and a transmembrane domain operably linked to the modified conantokin peptide domain, wherein the transmembrane domain is capable of directing the chimeric polypeptide to a cellular membrane in a target cell, wherein the modified conantokin peptide domain is a modified conantokin-P (con-P) peptide domain comprising the amino acid sequence as denoted by any one of SEQ ID NOs:
- 5-7.
Dependencies are inferred from the claim text.