Oligopeptide compounds and uses thereof
The present invention relates to novel agents, pharmaceutical compositions containing them, and their use in therapy, particularly anti-microbial and anti-cancer therapy. In particular, the present invention relates to novel peptide-based compounds based on SEQ ID NO: 40 which have surprisingly been shown to have inhibitory effects on the growth and/or viability of cells, particularly bacterial and cancer cells. Also provided are therapeutic and non-therapeutic methods which include the use of peptides of the invention.
1. A method of treating a bacterial infection and/or treating a neoplastic condition, the method comprising administering to a subject in need thereof an oligopeptidic compound comprising:
(i) the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40); or
(ii) an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40; wherein the compound has activity in inhibiting the growth and/or viability of bacterial cells and/or neoplastic cells, and further wherein the neoplastic condition is selected from brain cancer, breast cancer, melanoma, neuroblastoma, sarcoma, colon cancer, prostate cancer and a neoplastic condition of the skin.
2. The method of claim 1 , wherein the oligopeptidic compound has the sequence of SEQ ID NO: 40.
3. The method of claim 1 , wherein the oligopeptidic compound comprises one or more D-amino acids.
4. The method of claim 3 , wherein all the amino acids of the oligopeptidic compound are D-amino acids.
5. The method of claim 1 , wherein the oligopeptidic compound has one or more of the following properties:
a) a net charge at pH 7.0 of 10-13; b) a pI of 12 to 13; c) an average hydrophilicity of 0.7 to 1.0; and/or d) a ratio of hydrophilic residues to total number of residues of 45-60%.
6. The method of claim 1 , wherein the oligopeptidic compound is cytotoxic.
7. The method of claim 1 , wherein the oligopeptidic compound induces lysis and/or apoptosis of neoplastic cells.
8. The method of claim 1 , wherein the oligopeptidic compound is selectively cytotoxic towards neoplastic cells.
9. The method of claim 1 , wherein the neoplastic condition comprises a tumor and the size of the tumor is reduced.
10. The method of claim 1 , wherein when used in the treatment of the neoplastic condition, the oligopeptidic compound is locally delivered to the site of the neoplastic condition.
11. The method of claim 1 , wherein the method further comprises administering a second therapeutically active agent to the subject, wherein the second therapeutically active agent is selected from the group consisting of a chemotherapy agent, an anti-neoplastic agent, an antibiotic, an antiviral agent, and an antifungal agent.
12. The method of claim 1 , wherein the bacterial infection is caused by Staphylococcus or by enteric or coliform bacteria.
13. The method of claim 1 , wherein the bacterial infection is caused by Staphylococcus aureus, Escherichia coli , or an Enterococcus.
14. The method of claim 1 , wherein the bacterial infection is caused by bacteria from a genus selected from the group consisting of Escherichia, Staphylococcus, Enterococcus, Klebsiella, Pseudomonas , and Stenotrophomonas.
15. The method of claim 14 , wherein the bacteria is selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa , and Stenotrophomonas maltophilia.
16. The method of claim 1 , wherein the neoplastic condition of the skin is a non-malignant tumor of the skin.
17. An in vitro or ex vivo method for inhibiting the viability and/or growth of a bacterial cell, the method comprising contacting the bacterial cell with an oligopeptidic compound comprising:
(i) the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40); or
(ii) an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40;
wherein the compound has activity in inhibiting the growth and/or viability of the bacterial cell.
18. An in vitro or ex vivo method for inhibiting the viability and/or growth of cells of a neoplastic condition selected from the group consisting of brain cancer cells, breast cancer cells, melanoma cells, neuroblastoma cells, sarcoma cells, colon cancer cells, prostate cancer cells, and non-malignant skin tumor cells, the method comprising contacting the cells of the neoplastic condition with an oligopeptidic compound comprising:
(i) the amino acid sequence YGRKKRRQRRRGKTLRVAKAIYKRYIE (SEQ ID NO: 40); or
(ii) an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 40;
wherein the compound has activity in inhibiting the growth and/or viability of the cells of the neoplastic condition.