Use of peptide fragments of the calcium channel a-1 subunit, optionally comprising mutations, for screening molecules of therapeutic interest

A screening test for identifying molecules capable of disturbing the intramolecular interactions and the ionic activity of a α1 sub-unit from a calcium channel of a mammal, comprising:

• peptide fragments of a α1 sub-unit from a calcium channel of a mammal, said fragments corresponding to the I-II loop and/or to the III-IV loop of said α1 sub-unit, or corresponding to a peptide sequence derived from this I-II or III-IV loop, by substitution, and/or deletion, and/or addition of one or more amino acids, or corresponding to a peptide part of said I-II, or III-IV loop, or of a sequence derived from the latter, said derived sequence and said part of the I-II loop having the property of said I-II loop of binding to a β sub-unit and to the III-IV loop of said calcium channel, said derived sequence and said part of the III-IV loop having the property of said III-IV loop of binding to said I-II loop,
• or of mutated peptide sequences, derived by mutation of one or more amino acids of said peptide fragments of the I-II loop of the α1 sub-unit of the calcium channels to the extent that the mutation or mutations in question affect essential amino acids within the context of the expression of the calcium channels at the membrane surface, and/or of peptide sequences derived by mutation of one or more amino acids of said peptide fragments of the III-IV loop of the α1 sub-unit of the calcium channels, to the extent that the mutation or mutations in question affect essential amino acids within the context of the inactivation of the calcium channels,
• or of cells transformed by nucleotide sequences coding for said peptide fragments of the I-II loop and/or of the III-IV loop of the α1 sub-unit of the calcium channels, or coding for said mutated peptide sequences,
• for the implementation of a process for screening
• molecules restoring the number of calcium channels to normal in cell membranes where this number has abnormally reduced, namely screening β-like molecules capable of being used in the treatment of pathologies linked to an abnormal reduction in the number of calcium channels such as epilepsy, or neuronal degeneration,
• and/or molecules increasing the number of calcium channels in the cell membranes, namely screening β-like molecules capable of being used in the treatment of pathologies against which an increase in the number of calcium channels in the plasma membrane would have a beneficial effect, such as Parkinson's disease, insulin-dependent diabetes, or Lambert-Eaton myasthenic syndrome,
• and/or molecules restoring the number of calcium channels to normal in the cell membranes where this number has abnormally increased, namely screening molecules capable of being used in the treatment of pathologies linked to an abnormal increase in the number of calcium channels such as cardiac hypertrophy,
• and/or molecules reducing the number of calcium channels in the cell membranes, namely screening molecules capable of being used in the treatment of pathologies against which a reduction in the number of calcium channels in the plasma membrane would have a beneficial effect, such as epilepsy, hypertension, angina pectoris, or cerebral ischaemia,
• and/or molecules regulating the state of inactivation of the neuronal calcium channels involved in the release of neurotransmitters, namely screening molecules capable of being used in the stimulation or inhibition of neuronal communication, in particular in the treatment of pathologies against which a regulation of the state of inactivation of the neuronal calcium channels involved in the release of neurotransmitters would have a beneficial effect, such as epilepsy, ataxia, migraine, Parkinson's disease, or cerebral ischaemia.

A peptide comprising a peptide sequence chosen from:

• the sequences SEQ ID NO:
• 2 and SEQ ID NO:
• 4 in which at least one of Q in position 24, W in position 36, I in position 37, K in position 39, K in position 68, and K in position 69, is substituted by a natural or non-natural amino acid,
• the sequences SEQ ID NO:
• 2 and SEQ ID NO:
• 4 in which at least one of R in position 28, R in position 63, and R in position 64, is substituted by a natural or non-natural amino acid,
• the sequences SEQ ID NO:
• 2 and SEQ ID NO:
• 4 in which at least one of R in position 28, and E in position 29, is substituted by a natural or non-natural amino acid, in particular R28 is substituted by an alanine or by E, and E29 is substituted by an alanine,
• the following sequence SEQ ID NO:
• 15:
• QQIERELNGYMEWISKAE.