Methods and compositions relating to muscle specific...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/12 (2006.01) A01K 67/027 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C07K 16/18 (2006.01) G01N 33/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2425396

The present invention relates to the polypeptides known as calcineurin associated protein (calsarcin). Calsarcins-1, -2, and 3 bind to calcineurin, telethonin, and .alpha.-actinin, which provides a link between these molecules and the sarcomere. Sarcomeric dysfunction ultimately leads to activation of calcineurin and consequent hypertrophic cardiomyopathy. Thus, methods utilizing calsarcin as it regards these medical conditions are herein provided and include screening for peptides which interact with calsarcin, screening for modulators of calsarcin binding to calcineurin or .alpha.-actinin, methods to modulate calcineurin activity, methods to inhibit calcineurin activation of gene transcription and methods for treating cardiac hypertrophy, heart failure and Type II diabetes.

La présente invention concerne les polypeptides connus sous le nom générique de protéine associée à la calcineurine (calsarcine). La calsarcine-1, -2 et -3 se fixe sur la calcineurine, la téléthonine et l'alpha actinine, ce qui permet d'obtenir une liaison entre ces molécules et le sarcomère. Le dysfonctionnement sarcomérique conduit en dernier lieu à l'activation de la calcineurine et à une cardiomyopathie hypertrophique. Par conséquent, l'invention concerne des méthodes employant la calsarcine, destinées à remédier à ces états pathologiques, comprenant des étapes de sélection de peptides qui interagissent avec la calsarcine et des étapes de sélection de modulateurs de la calsarcine se fixant sur la calcineurine ou l'alpha actinine. L'invention concerne également des méthodes destinées à la modulation de l'activité de la calcineurine, des méthodes permettant d'inhiber l'activation calcineurinique de la transcription du gène et des méthodes destinées au traitement de l'hypertrophie cardiaque, de l'arrêt cardiaque et du diabète de type II.

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