Glycosyltransferase proteins
OwnerStephen Cohen, Katja Bruckner +2inventors
InventorsStephen Cohen, Katja Bruckner, Henrik Clausen, Birgit Keck
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Abstract
The invention is based on the discovery that various proteins, such as Fringe, Brainiac and homologues and orthologues thereof, possess glycosyltransferase activity. Fringe and Brainiac have been found to possess glycosyltransferase activity in transfering sugar residues onto certain proteins, so affecting the binding of effector molecules to these proteins. This discovery allows the design of drug molecules that specifically target this interaction, and has implications for the treatment of various diseases.
Claims20
Use of a Brainiac protein, or a fragment, or functional equivalent of a Brainiac protein, as a glycosyltransferase, wherein said Brainiac protein, fragment thereof, or functional equivalent thereof acts to elongate a mannose residue linked to a protein via an O-linked glucose residue or via a ceramide in a glycolipid.
Use of a ligand of a Brainiac protein as a glycosyltransferase inhibitor, wherein said ligand is effective to prevent elongation of a mannose residue linked to a protein via an O-linked glucose residue or via a ceramide in a glycolipid.
Use of a Brainiac protein, or a fragment or functional equivalent of a Brainiac protein, or of a ligand of a Brainiac protein, in the manufacture of a medicament for the treatment of a disease caused by a protein containing one or more EGF-like modules, in which said disease is characterised by a deficiency in glycosylation of mannose residues linked to the protein via an O-linked glucose residue or in glycosylation of mannose residues linked to via a ceramide in a glycolipid.
A method of treating a disease caused by an EGF-like module containing protein, in which there is a deficiency in glycosylation of mannose residues linked to the protein via an O-linked glucose residue or in glycosylation of mannose residues linked to via a ceramide in a glycolipid, said method comprising administering to a patient a Brainiac protein, or a fragment, or functional equivalent of a Brainiac protein, or a ligand of a Brainiac protein.
A Brainiac protein, or a fragment or functional equivalent of a Brainiac protein, for use as a glycosyltransferase, wherein said Brainiac protein, fragment thereof, or functional equivalent thereof acts to elongate a mannose residue linked to a protein via an O-linked glucose residue or via a ceramide in a glycolipid.
A method of transferring a N-acetylglucosamine moiety onto a mannose substrate, whether free or attached to a lipid, carbohydrate or protein, comprising the step of incubating a Brainiac protein, or a fragment, or functional equivalent of a Brainiac protein with said substrate.
A method of screening for a ligand capable of modulating the activity of a Brainiac protein, said method comprising the steps of
- a) contacting a candidate ligand with said Brainiac protein or a fragment thereof;
- and
- b) testing the effect of the ligand on the glycosyltransferase activity of said Brainiac protein, wherein said Brainiac protein or fragment thereof acts to elongate a mannose residue linked to a protein via an O-linked glucose residue or via a ceramide in a glycolipid.
A method of screening for a ligand of a substrate for a Brainiac protein, said method comprising the steps of:
- a) contacting a candidate ligand with said substrate in the presence of a Brainiac protein;
- and
- b) testing the effect of the ligand on the extent of elongation of mannose residues linked to a protein substrate via an O-linked glucose residue or via a ceramide in a glycolipid substrate.
A method for the identification of a gene that is implicated in a disease or physiological condition in which Brainiac function plays a role, said method comprising the steps of:
- a) comparing:
- i) the transcriptome or proteome of a first cell type;
- with
- ii) the transcriptome or proteome of a second cell type in which the expression or activity of the Brainiac protein is altered in comparison to the first cell type;
- and
- b) identifying as the gene implicated in the disease or condition, a gene encoding a protein whose level of glycosylation differs between the two cell types, wherein said level of glycosylation is the extent of elongation of mannose residues linked to a protein via an O-linked glucose residue or via a ceramide in a glycolipid.
Dependencies are inferred from the claim text.