Inhibiting interaction between hif-1.alpha. and p300/cbp...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 7/06 (2006.01) A61K 38/08 (2006.01)

Patent

CA 2737614

The present invention relates to peptides having one or more stable, internally constrained .alpha.-helices, and that include a sequence that mimics at least a portion of the C-terminal transactivation domain of HIF-1.alpha.. Also disclosed are pharmaceutical compositions containing these peptides and methods of using these peptides, for example to reduce gene transcription, treat or prevent disorders mediated by interaction of HIF-1.alpha. with CREB-binding protein and/or p300, reduce or prevent angiogenesis in a tissue, induce apoptosis, decrease cell survival and/or proliferation, and identify potential ligands of CREB-binding protein and/ or p300.

La présente invention concerne des peptides comprenant une ou plusieurs hélices a stables à contrainte interne et qui comprennent une séquence qui imite au moins une partie du domaine de transactivation C-terminal de HIF-la. Elle concerne également des compositions pharmaceutiques contenant ces peptides et des procédés d'utilisation de ces peptides, par exemple pour réduire la transcription de gènes, traiter ou prévenir des affections médiées par l'interaction de HIF-la avec une protéine liant CREB et/ou p300, réduire ou prévenir l'angiogenèse dans un tissu, induire l'apoptose, réduire la survie et/ou la prolifération cellulaire, et identifier des ligands potentiels de protéine liant CREB et/ou de p300.

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