DPP8 and DPP9 peptide inhibitors
AssigneeGeorg-August-Universität Göttingen Stiftung Öffentlichen Rechts
InventorsRuth Geiss-Friedlander, Esther Pilla
Life of this patent
Estimating the term…
Abstract
The present invention relates to non-competitive allosteric peptide inhibitors of DPP9 and/or DPP8, competitive peptides binding to SUMO1, nucleic acid molecules and expression vectors coding said peptide inhibitors, host cells expressing said inhibitors, kits comprising said inhibitors, as well as methods of producing said inhibitors, and uses of said peptide inhibitors; as further defined in the Claims.
Claims17
A peptide of 8 to 20 amino acids length, comprising the N-terminal sequence
- Xaa1-Leu-Arg-Phe-Leu-Xaa6-Xaa7-Xaa8,
- wherein Xaa1 is selected from Ser and Thr,
- wherein Xaa6 is selected from Phe, Tyr, Trp, Val and Ile,
- wherein Xaa 7 is selected from Ala and Glu, and
- wherein Xaa8 is selected from Gly and Ala (SEQ ID NO:
- 48);
- with the proviso that if Xaa6 is Phe, then Xaa7 is Ala or Xaa1 is Thr;
- wherein the peptide is a non-competitive allosteric inhibitor of a dipeptidyl peptidase selected from DPP9, DPP8, and a combination of DPP8 and DPP9.
A polypeptide, comprising, fused to the N-terminus, a peptide of 8 to 20 amino acids length, comprising the N-terminal sequence Xaa1-Leu-Arg-Phe-Leu-Xaa6-Xaa7-Xaa8,
- wherein Xaa1 is selected from Ser and Thr,
- wherein Xaa6 is selected from Phe, Tyr, Trp, Val and Ile,
- wherein Xaa7 is selected from Ala and Glu, and
- wherein Xaa8 is selected from Gly and Ala (SEQ ID NO:
- 48);
- with the proviso that if Xaa6 is Phe, then Xaa7 is Ala or Xaa1 is Thr;
- wherein the peptide is a non-competitive allosteric inhibitor of a dipeptidyl peptidase selected from DPP9, DPP8, and a combination of DPP8 and DPP9.
A peptide having the sequence Val-Glu-Xaa3-Ile-His-Val-Xaa7-Ser-Pro-Xaa10-Leu-Glu-Xaa13-Arg-Xaa15-Xaa16-Asp-Ser-Xaa19-Arg,
- wherein Xaa3 is any amino acid other than Val or Ile,
- wherein Xaa7 is selected from Pro and Thr,
- wherein Xaa10 is selected from Ala and Met,
- wherein Xaa13 is selected from Glu and Thr,
- wherein Xaa15 is selected from Lys and Arg,
- wherein Xaa16 is selected from Thr and Ala, and
- wherein Xaa19 is selected from Tyr and Phe, as represented by SEQ ID NO:
- 49,
- wherein the peptide competitively inhibits binding to the E67-interacting loop (EIL) of SUMO-1.
A polypeptide comprising
- a peptide having the sequence
- Val-Glu-Xaa3-Ile-His-Val-Xaa7-Ser-Pro-Xaa10-Leu-Glu-Xaa13-Arg-Xaa15-Xaa16-Asp-Ser-Xaa19-Arg,
- wherein Xaa3 is any amino acid other than Val or Ile,
- wherein Xaa7 is selected from Pro and Thr,
- wherein Xaa10 is selected from Ala and Met,
- wherein Xaa13 is selected from Glu and Thr,
- wherein Xaa15 is selected from Lys and Arg,
- wherein Xaa16 is selected from Thr and Ala, and
- wherein Xaa19 is selected from Tyr and Phe, as represented by SEQ ID NO:
- 49,
- wherein the peptide competitively inhibits binding to the E67-interacting loop (EIL) of SUMO-1;
- and
- wherein the polypeptide is not DPP8 or DPP9.
A method for the treatment of cancer, comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising (i) a peptide of 8 to 20 amino acids length, comprising the N-terminal sequence Xaa1-Leu-Arg-Phe-Leu-Xaa6-Xaa7-Xaa8,
- wherein Xaa1 is selected from Ser and Thr,
- wherein Xaa6 is selected from Phe, Tyr, Trp, Val and Ile,
- wherein Xaa7 is selected from Ala and Glu, and
- wherein Xaa8 is selected from Gly and Ala (SEQ ID NO:
- 48),
- with the proviso that if Xaa6 is Phe, then Xaa7 is Ala or Xaa1 is Thr,
- wherein the peptide is a non-competitive allosteric inhibitor of a dipeptidyl peptidase selected from DPP9, DPP8, and a combination of DPP8 and DPP9;
- or
- (ii) a polypeptide, comprising, fused to the N-terminus, the peptide according to (i);
- and
- a pharmaceutically acceptable carrier, excipient or diluent.
Dependencies are inferred from the claim text.