Flagellin related polypeptides and uses thereof
The use of flagellin and flagellin related polypeptides for the protection of mammals from the effects of apoptosis is described.
1. A composition comprising a Salmonella flagellin polypeptide of the following formula:
amino terminal domain-linker-carboxyl terminal domain,
wherein
(a) the amino terminal domain is an amino acid sequence that is at least 95% identical to amino acids 1-174 of SEQ ID NO: 1;
(b) the carboxyl terminal domain is an amino acid sequence of amino acids 402-505 of SEQ ID NO: 1 or 402-450 of SEQ ID NO: 1 and
(c) the linker is the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4; and
wherein the flagellin polypeptide is capable of inducing NF-kB activity and has an immunogenicity that is less than 5% compared to the immunogenicity of SEQ ID NO: 1.
2. The composition of claim 1 , wherein the carboxyl terminal domain is an amino acid sequence of amino acids 402-505 of SEQ ID NO: 1.
3. The composition of claim 1 , wherein the carboxyl terminal domain is an amino acid sequence of amino acids 402-450 of SEQ ID NO: 1.
4. The composition of claim 1 , wherein the amino terminal domain is an amino acid sequence of amino acids 1-174 of SEQ ID NO: 1.
5. The composition of claim 1 , wherein the amino terminal domain is an amino acid sequence of amino acids 54-163 of SEQ ID NO: 1.
6. The composition of claim 1 , wherein the composition further comprises a radioprotectant.
7. The composition of claim 6 , wherein the radioprotectant is selected from the group consisting of an antioxidant, amifostine, vitamin E, a cytokine, a stem cell factor, a growth factor, keratinocyte growth factor, a steroid, 5-androstenediol, and ammonium trichloro(dioxethylene-O,O′)tellurate.
8. A composition comprising a Salmonella flagellin polypeptide of the following formula:
amino terminal domain-linker-carboxyl terminal domain,
wherein
(a) the amino terminal domain is an amino acid sequence that is at least 95% identical to amino acids 1-174 of SEQ ID NO: 1 and
(b) the carboxyl terminal domain is an amino acid sequence of amino acids 402-505 of SEQ ID NO: 1 or 402-450 of SEQ ID NO: 1, and
(c) the linker is the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4;
wherein the flagellin polypeptide is capable of inducing NF-kB activity and has a molecular weight of around 60% of SEQ ID NO: 1.
9. The composition of claim 8 , wherein the carboxyl terminal domain is an amino acid sequence of amino acids 402-505 of SEQ ID NO: 1.
10. The composition of claim 8 , wherein the carboxyl terminal domain is an amino acid sequence of amino acids 402-450 of SEQ ID NO: 1.
11. The composition of claim 8 , wherein the amino terminal domain is an amino acid sequence of amino acids 1-174 of SEQ ID NO: 1.
12. The composition of claim 8 , wherein the amino terminal domain is an amino acid sequence of amino acids 54-163 of SEQ ID NO: 1.
13. The composition of claim 8 , wherein the composition further comprises a radioprotectant.
14. The composition of claim 13 , wherein the radioprotectant is selected from the group consisting of an antioxidant, amifostine, vitamin E, a cytokine, a stem cell factor, a growth factor, keratinocyte growth factor, a steroid, 5-androstenediol, and ammonium trichloro(dioxethylene-O,O′)tellurate.