C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 9/50 (2006.01) A61K 31/7088 (2006.01) A61K 38/48 (2006.01) A61K 48/00 (2006.01) C12N 9/64 (2006.01) C12Q 1/37 (2006.01) G01N 33/53 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2448828
The present invention provides methods and compositions for inhibiting angiogenesis, tumor growth and treating disease states using a peptide that contains a specific amino acid sequence of matrix metalloproteinase 2 (MMP-2). In one embodiment, the invention provides a peptide, which comprises the amino acid sequence Ile-Phe-Ala-Gly-Asp-Lys-Phe-Trp-Arg, preferably flanked by cysteine residues at the amino and carboxy termini. Additionally, the invention provides compositions for inhibiting angiogenesis or tumor growth or for treating disease states comprising organic and non-peptidic mimetics based on the above amino acid sequence as well as optimized sequences flanking the region of MMP-2 within which the sequence lies. Also provided are methods for detecting angiogenesis, tumorous tissue, metastases, and tumor invasion into a tissue by contacting a composition of the invention with a tissue and methods for screening compositions of the invention.
L'invention concerne des procédés et des compositions d'inhibition de l'angiogenèse, de la croissance tumorale et du traitement de maladies faisant intervenir un peptide contenant une séquence d'acides aminés spécifique d'une métalloprotéase matricielle 2 (MMP-2). Selon un mode de réalisation, l'invention concerne un peptide renfermant la séquence d'acides aminés Ile-Phe-Ala-Gly-Asp-Lys-Phe-Trp-Arg, présentant de préférence de restes de cystéine aux terminaisons de l'acide aminé et du groupe carboxy. Par ailleurs, l'invention concerne des compositions d'inhibition de l'angiogenèse ou de la croissance tumorale ou pour le traitement de maladies ayant des aspects mimétiques organiques et non peptidiques inspirés de la séquence d'acides aminés ainsi que des séquences optimisées contenues dans la zone de la MPP-2 dans laquelle se trouve la séquence. Font également l'objet de cette invention des procédés de détection de l'angiogenèse, de tissus cancéreux, de métastases et d'invasion tumorale dans un tissu par la mise en contact d'une composition avec un tissu ainsi que des procédés de criblage de compositions de cette invention.
Brooks Peter C.
Rodriguez Dorothy
Oyen Wiggs Green & Mutala Llp
University Of Southern California
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