Maurocalcine, analogues thereof and their therapeutical uses

Details Maurocalcine, analogues thereof and their therapeutical uses Maurocalcine, analogues thereof and their therapeutical uses

C - Chemistry, Metallurgy

07

K

C07K 14/435 (2006.01) A61K 38/17 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2401963

Maurocalcine, a novel toxin isolated from the venom of the Tunisian chactidae scorpion Scorpio maurus palmatus, has the amino acid sequence GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR (SEQ. ID. No. 1). It potently and reversibly modifies channel gating behaviour of type 1 ryanodine receptor (RyR1) by inducing prominent subconductance behavior. Maurocalcine and its bioactive structural analogues - preferably those containing the KKCKRR motif corresponding to part of the II-III loop of the alpha1S subunit of the voltage- dependent skeletal muscle calcium channel dihydropyridine receptor - appear to possess a therapeutic potential, notably as candidate immuno-suppressive drugs, and for the treatment of pathologies in humans that may involve a dysfunction of calcium channels.

Selon l'invention, la maurocalcine, nouvelle toxine isolée à partir du venin du scorpion tunisien de la famille des chactidae Scorpio maurus palmatus, possède la séquence d'acides aminés GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR (SEQ. ID. No. 1) et peut modifier efficacement et de manière réversible le comportement d'activation de canal du récepteur de ryanodine de type 1 en provoquant un comportement de sous-conductance remarquable. La maurocalcine et ses analogues structurels bioactifs, de préférence ceux contenant le motif KKCKRR correspondant à une partie de la boucle II-III de la sous-unité alpha1S du récepteur de dihydropyridine du canal calcium des muscles squelettiques dépendant de la tension, semblent posséder un potentiel thérapeutique, notamment comme immunosuppresseurs candidats, ainsi que pour le traitement de pathologies pouvant impliquer un dysfonctionnement des canaux calcium chez l'homme.

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