Pancreatic polypeptide family motifs, polypeptides and methods comprising the same
The present invention provides novel Pancreatic Polypeptide Family (“PPF”) polypeptides and methods for their use.
1. A PPF polypeptide comprising an amino acid sequence of Formula (VII) (SEQ ID NO: 482):
Xaa 1 Xaa 2 Pro Xaa 4 Pro Xaa 6 His Pro Xaa 9 Xaa 10
Xaa 11 Xaa 12 Xaa 13 Xaa 14 Xaa 15 Xaa 16 Xaa 17 Ala
Xaa 19 Tyr Xaa 21 Xaa 22 Xaa 23 Leu Xaa 25 Xaa 26 Xaa 27
Xaa 28 Xaa 29 Xaa 30 Xaa 31 Thr Arg Gln Arg Tyr
wherein:
Xaa 1 is Tyr or absent;
Xaa 2 is Ile, Pro, or absent;
Xaa 4 is Lys, BH-modified Lys, Ala, Ser, or Arg;
Xaa 6 is Glu, Gln, Ala, Asn, Asp, or Val;
Xaa 9 is Gly or Ala;
Xaa 10 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;
Xaa 11 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;
Xaa 12 is Ala or Pro;
Xaa 13 is Ser or Pro;
Xaa 14 is Pro, Ala, or Ser;
Xaa 15 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;
Xaa 16 is Glu or Asp;
Xaa 17 is Leu or Ile;
Xaa 19 is Arg, Lys, BH-modified Lys, Gln, or N(Me)Ala;
Xaa 21 is Tyr, Ala, Phe, Lys, or BH-modified Lys;
Xaa 22 is Ala or Ser;
Xaa 23 is Ser, Ala, or Asp;
Xaa 25 is Arg, Lys or BH-modified Lys;
Xaa 26 is His, Ala, or Arg;
Xaa 27 is Tyr, or Phe;
Xaa 28 is Leu or Ile;
Xaa 29 is Asn, or Gln;
Xaa 30 is Leu or Met; and
Xaa 31 is Val, Ile, or Leu.
2. The PPF polypeptide of claim 1 , wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 266, 437, 438, 439, 442, 462, 469, 470, 471 and 472.
3. The PPF polypeptide of claim 1 , wherein said PPF polypeptide further comprises an N-terminal cap.
4. The PPF polypeptide of claim 2 , wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 437, 462, 469, 470 and 472.
5. The PPF polypeptide of claim 1 , wherein said polypeptide is linked to one or more water-soluble polymers.
6. The PPF polypeptide of claim 5 , wherein said polymer is selected from at least one of the group consisting of polyethylene glycol and a fatty acid molecule, wherein said polymer is linked to the N- or C-terminus of the polypeptide, or the side chain of a lysine or serine amino acid residue within the sequence of the polypeptide.