Brain-derived membrane-associated crf binding proteins

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/16 (2006.01) C07K 7/08 (2006.01) C07K 14/72 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2175373

Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.

L'invention se rapporte à des protéines de liaison du facteur de libération de la corticotrophine (SLC), isolées, pratiquement pures associées à une membrane et dérivées du cerveau d'un mammifère et à des fragments biologiquement actifs de celles-ci, ainsi qu'à des fragments d'ADN isolés et purifiés qui codent les protéines de liaison du SLC ou leurs fragments biologiquement actifs, ou des homologues d'autres espèces mammaliennes. En administrant une quantité de cette protéine de liaison du SLC ou d'un fragment de celle-ci efficace pour moduler l'activation du récepteur, il est possible de moduler l'action du SLC sur (a) le cerveau et le système nerveux, (b) l'hypophyse notamment dans la production de la corticotrophine, de l'endorphine bêta et de l'hydrocortisone, (c) les sites d'inflammation, (d) le placenta, (e) les glandes surrénales, (f) les gonades ou (g) les voies gastro-intestinales. L'administration d'un fragment N-terminal de la protéine augmente la densité du site de liaison du SLC et module ainsi son effet biologique <u>in vivo</u>.

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