Glucagon-like peptide-2 analogs
Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.
1. An intestinotrophic GLP-2 analog, comprising SEQ ID NO: 2, wherein
position 2 of SEQ ID NO: 2 consists of an amino acid other than Ala,
positions 5-9, 11-18, and 21-23 of SEQ ID NO: 2 are unmodified,
position 1 of SEQ ID NO: 2 optionally consists of an amino acid other than His;
position 3 of SEQ ID NO: 2 optionally consists of an amino acid other than Asp;
position 4 of SEQ ID NO: 2 optionally consists of an amino acid other than Gly;
position 10 of SEQ ID NO: 2 optionally consists of an amino acid other than Met;
position 19 of SEQ ID NO: 2 optionally consists of an amino acid other than Ala;
position 20 of SEQ ID NO: 2 optionally consists of an amino acid other than Arg; and
position 24 of SEQ ID NO: 2 optionally consists of an amino acid other than Asn.
2. A pharmaceutical composition comprising the GLP-2 analog of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
3. The GLP-2 analog of claim 1 , wherein the amino acid at position 1 is Tyr or Ala.
4. The GLP-2 analog of claim 1 , wherein the amino acid at position 2 is one of the following: D-Ala, Gly, Val, t-Butyl-Gly, Asp, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Tyr, Pen, β-Ala, α-Abu, Nval, PhGly, or Aib.
5. The GLP-2 analog of claim 1 , wherein the amino acid at position 3 is Glu or Ala.
6. The GLP-2 analog of claim 1 , wherein the amino acid at position 4 is Ala.
7. The GLP-2 analog of claim 1 , wherein the amino acid at position 10 is one of the following: Val, Ile, Asn, Glu, Gln, Tyr, Phe, Leu, Nle, Ala, Ser, or Gly.
8. The GLP-2 analog of claim 1 , wherein the amino acid at position 19 is Thr.
9. The GLP-2 analog of claim 1 , wherein the amino acid at position 20 is Lys or Ala.
10. The GLP-2 analog of claim 1 , wherein the amino acid at position 24 is Ala.
11. The GLP-2 analog of claim 1 wherein the amino acid at position 2 is Gly.