Peptide analogues of GIP for treatment of diapetes, insulin resistance and obesity
AssigneeUUTech Limited
InventorsVictor Gault, Finbarr O'Harte, Nigel Irwin, Peter Flatt
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Abstract
The present invention provides peptide analogues which are antagonists of gastric inhibitory peptide (GIP). The peptides, based on GIP 1-42 include substitutions and/or modifications which have enhanced resistance to degradation by the enzyme dipeptidyl peptidase IV (DPP IV). The invention also provides a process of N terminally modifying GIP and the use of the peptide analogues for treatment of diabetes.
Claims38
A peptide analogue of GIP(1-42) (SEQ ID NO:1), comprising at least 12 amino acid residues from the N-terminal end of GIP(3-42).
A peptide analogue of GIP(1-42) (SEQ ID NO:
- 1), comprising at least 12 amino acid residues from the N-terminal end of GIP(1-42) and having an amino acid substitution at Glu3.
A peptide analogue of GIP(1-42) (SEQ ID NO:
- 1), comprising at least 12 amino acid residues from the N-terminal end of GIP(1-42), and having an amino acid modification at amino acid residues 1, 2 or 3.
A peptide analogue of GIP(1-42) (SEQ ID NO:1), wherein the analogue comprises:
- a base peptide consisting of one of the following:
- GIP(1-12), GIP(1-13), GIP(1-14), GIP(1-15), GIP(1-16), GIP(1-17), GIP(1-18), GIP(1-19), GIP(1-20), GIP(1-21), GIP(1-22), GIP(1-23), GIP(1-24), GIP(1-25), GIP(1-26), GIP(1-27), GIP(1-28), GIP(1-29), GIP(1-30), GIP(1-31), GIP(1-32), GIP(1-33), GIP(1-34), GIP(1-35), GIP(1-36), GIP(1-37), GIP(1-38), GIP(1-39), GIP(1-40), GIP(1-41) and GIP(1-42);
- which possesses one or more of the following modifications:
- an amino acid substitution at one or more of the residues;
- an amino acid substitution of lysine for one or more or the residues;
- an amino acid substitution at Glu3;
- a modification by fatty acid addition at an epsilon amino group of at least one lysine residue;
- and
- a modification by N-terminal acetylation.
A peptide analogue of GIP(1-42) (SEQ ID NO:1), comprising at least 12 amino acid residues from the N-terminal end of GIP(3-42), wherein the peptide analogue is resistant to degradation by enzyme DPP IV when compared to naturally-occurring GIP.
A peptide analogue of GIP(1-42) (SEQ ID NO:
- 1), comprising at least 12 amino acid residues from the N-terminal end of GIP(1-42) and having an amino acid substitution at Glu3, wherein the peptide analogue is resistant to degradation by enzyme DPP IV when compared to naturally-occurring GIP.
A peptide analogue of GIP(1-42) (SEQ ID NO:1), comprising at least 12 amino acid residues from the N-terminal end of GIP(3-42), wherein the peptide analogue modulates insulin secretion.
A peptide analogue of GIP(1-42) (SEQ ID NO:1), comprising at least 12 amino acid residues from the N-terminal end of GIP(1-42) and having an amino acid substitution at Glu3, wherein the peptide analogue modulates insulin secretion.
Dependencies are inferred from the claim text.