C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/47 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01) C07K 19/00 (2006.01) C12N 5/18 (2006.01) C12N 5/22 (2006.01) C12Q 1/26 (2006.01) G01N 33/53 (2006.01) G01N 33/573 (2006.01) G01N 33/68 (2006.01)
Patent
CA 2460700
A target asparagine residue of HIF 1 alpha and 2 alpha is hydroxylated at high oxygen tension to render HIF as a weak transcription factor. An asparagine hydroxylase hydroxylation motif and binding motif is proposed. A method of screening for agonists or antagonists of an asparagine hydroxylase is also proposed and involves mixing peptides or proteins having the hydroxylation and or the binding motif with asparagine hydroxylase and a candidate agonist or antagonist. The extent of inhibition or enhancement of binding; level of asparagine hydroxylation or transactivation may be measured depending on the nature of the protein or peptide. Additionally altered proteins resistant to hydroxylation are described as are nucleic acids encoding such proteins.
Selon l'invention, un résidu d'une asparagine cible de HIF 1 alpha et 2 alpha est hydroxylée à une tension en oxygène élevée afin que HIF devienne un facteur de transcription faible. L'invention décrit un motif de fixation et un motif d'hydroxylation de l'hydroxylase d'une asparagine. Un procédé de criblage d'agonistes et d'antagonistes de l'hydroxylase d'une asparagine est aussi décrit. Ce procédé consiste à mélanger des peptides ou des protéines comprenant le motif d'hydroxylation et/ou de fixation avec l'hydroxylase asparagine et un agoniste ou antagoniste candidat. L'extension de l'inhibition et l'amélioration de la fixation, et le niveau d'hydroxylation ou la transactivation de l'asparagine peuvent être mesurés en fonction de la nature de la protéine ou du peptide. L'invention concerne en outre, des protéines modifiées résistant à l'hydroxylation, ainsi que les acides nucléiques codant ces protéines.
Gorman Jeffrey J.
Lando David
Linke Sarah
Peet Daniel J.
Whitelaw Murray L.
Adelaide Research & Innovation Pty Ltd
Ridout & Maybee Llp
LandOfFree
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