C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/57 (2006.01) C07H 21/00 (2006.01) C07K 7/08 (2006.01) C07K 16/40 (2006.01) C12N 9/48 (2006.01) C12N 9/64 (2006.01) C12Q 1/37 (2006.01) C12Q 1/68 (2006.01) G01N 33/543 (2006.01) G01N 33/573 (2006.01) G01N 33/68 (2006.01)
Patent
CA 2200354
An aminopeptidase which cleaves insulin has been purified from GLUT-4- containing vesicles and cloned. The peptidase has a measured mass of approximately 165 kD, but is 110 kD in its deglycosylated state. It has a predicted mass of 117,239 Daltons based on the amino acid sequence predicted from the cDNA of the figure (SEQ ID NOs: 15 and 16). It includes peptides having the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly- Xaa-Pro-Xaa-Met (SEQ ID NO: 2), and binds with antibodies produced against the peptide identified as (SEQ ID NO: 1). Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.
On a purifié une aminopeptidase qui scinde l'insuline, à partir de vésicules contenant des protéines GLUT-4 et on l'a clonée. La peptidase a une masse mesurée d'environ 165 kD, mais de 110 kD à l'état déglycosylé. La masse théorique est de 117.239 Daltons, si on se base sur la séquence des acides aminés produite par l'ADN complémentaire de la Figure (SEQ ID Nos: 15 et 16). Elle comprend les peptide ayant les séquences d'acides aminés Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala-(SEQ ID NO:1) et Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Met (SEQ ID NO: 2) et se fixe à des anticorps produits contre le peptide identifié comme (Seq ID No: 1). On revendique également des modulateurs de l'activité de l'aminopeptidase et un procédé pour traiter des symptômes de résistance à l'insuline, en particulier le diabète, par l'administration d'un tel modulateur.
Clairmont Kevin B.
Guralski Donna
Haigh Wallace
Hart John T.
Knowles William J.
Borden Ladner Gervais Llp
Corporation Bayer
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