Peptides for management of lactation
The present invention provides novel short peptides that are highly effective in inducing involution in a mammary gland of a lactating mammal and cessation of milk production by the gland. The invention further provides pharmaceutical composition comprising the peptides and methods of use thereof including for treating microbial infection in a mammary gland.
1. A synthetic or recombinant peptide comprising a sequence of 4-7 amino acids of the formula X 1(n)- Ser(P)-Ser(P)-Ser(P)-X 2 (m)- (SEQ ID NO:1), where Ser(P) represents phosphorylated serine, wherein at least one of X 1 and X 2 is a positively charged amino acid and wherein n+m=1-4, wherein the formula of SEQ ID NO:1 further comprises a blocking group at the C-terminus.
2. The synthetic or recombinant peptide of claim 1 , wherein the positively charged amino acid is selected from the group consisting of lysine, arginine and histidine.
3. The synthetic or recombinant peptide of claim 2 , wherein the positively charged amino acid is lysine.
4. The synthetic or recombinant peptide of claim 1 , wherein the blocking group is selected from amid and ester.
5. The synthetic or recombinant peptide of claim 1 , said peptide comprises the amino acid sequence set forth in any one of SEQ ID NOs: 2-9.
6. The synthetic or recombinant peptide of claim 5 , said peptide consists of SEQ ID NO:2.
7. The synthetic or recombinant peptide of claim 4 , said peptide comprises the amino acid sequence set forth in SEQ ID NO:12.
8. A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of a synthetic or recombinant peptide comprising a sequence of 4-7 amino acids of the formula X 1(n)- Ser(P)-Ser(P)-Ser(P)-X 2(m) (SEQ ID NO:1), where Ser(P) represents phosphorylated serine, wherein at least one of X 1 and X 2 is a positively charged amino acid and wherein n+m=1-4, wherein the formula of SEQ ID NO:1 further comprises a blocking group at the C-terminus.
9. The pharmaceutical composition of claim 8 , wherein the positively charged amino acid of SEQ ID NO:1 is selected from the group consisting of lysine, arginine and histidine.
10. The pharmaceutical composition of claim 8 , wherein the blocking group is selected from amid and ester.
11. The pharmaceutical composition of claim 8 , wherein said composition comprises a peptide comprising the amino acid sequence set forth in any one of SEQ ID NOs 2-9 or a combination thereof.
12. The pharmaceutical composition of claim 10 , wherein said composition comprises a peptide having the amino acid sequence of SEQ ID NO:12.
13. A method of inducing a transient cessation of milk production, a persistent cessation of milk production or involution in a mammary gland of a lactating mammal, comprising administering to a lactating mammal in need thereof a pharmaceutical composition comprising an effective amount of the synthetic or recombinant peptide of claim 1 .
14. The method of claim 13 , wherein the positively charged amino acid of SEQ ID NO: 1 is selected from the group consisting of lysine, arginine and histidine.
15. The method of claim 13 , wherein the peptide of the formula of SEQ ID NO: 1, wherein the blocking group is selected from amid and ester.
16. The method of claim 13 , wherein the lactating mammal is selected from a lactating livestock animal and a lactating human.
17. The method of claim 13 , wherein the pharmaceutical composition is administered while the mammary gland is lactating.
18. The method of claim 13 , wherein the pharmaceutical composition is administered at the same time milking or nursing is ceasing.
19. The method of claim 13 , wherein the pharmaceutical composition further comprises an anti-microbial agent selected from the group consisting of antibiotic, bactericide, steroidal and non-steroidal anti-inflammatory agents, or an immunomodulator and a vaccine.
20. A method for treating or inhibiting a microbiological infection, comprising administering to a lactating animal a pharmaceutical composition comprising an effective amount of the synthetic or recombinant peptide of claim 1 .