Therapeutic pore-forming peptides
AssigneeGreenville Hospital System
InventorsXianxhang Yu, Thomas E. Wagner
Life of this patent
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Abstract
A class of procytotoxic agents is characterized by a capability to kill with target cell-specificity. Such an aspect can be a pore-forming protein which has at least one lysine residue, modified by a peptide linkage to an amino acid residue, via the epsilon amino group. These agents are useful in treating cancer, especially prostate cancer.
Claims23
A procytotoxin comprising a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue, wherein said peptide without said modification is a cytotoxic peptide, and wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and wherein the cytotoxic peptide is a pore-forming cytolytic peptide.
A procytotoxin comprising a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue, wherein said peptide without said modification is a cytotoxic peptide, and wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and wherein said procytotoxin comprises a structure selected from the group consisting of:
- N-Gly-Phe-Ile-Ala-Thr-Leu-Cys-Thr-Lys-Val- Leu-Asp-Phe-Gly-Ile-Asp-Lys-Leu-Ile-Gln-Leu-Ile-Glu-Asp-Lys([ε-γ]-Glu-[α-γ]-Glu)-CONH2 (SEQ ID NO:
- 8) and NH2-Gly-Ile-Gly-Ala-Val-Leu-Lys-Val-Leu-Thr-Thr-Gly-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-Lys-([ε-γ]-Glu-[α-γ]-Glu)-Arg-Lys([ε-γ]-Glu-[α-γ]-Glu)-Arg-Gln-Gln-COOH (SEQ ID NO:
- 12).
A method for selectively destroying a target cell that is a cancer cell, comprising contacting the target cell with a procytotoxin, which comprises a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue, wherein said peptide without said modification is a cytotoxic peptide, and wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and wherein the cytotoxic peptide is a pore-forming cytolytic peptide.
A method for selectively destroying a target cell that is a cancer cell, comprising contacting the target cell with a procytotoxin, which comprises a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue, wherein said peptide without said modification is a cytotoxic peptide, and wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and the procytotoxin comprises the structure NH2-Gly-Ile-Gly-Ala-Val-Leu-Lys-Val-Leu-Thr-Thr-Gly-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-Lys ([ε-γ]-Glu- [α-γ]-Glu)-Arg-Lys([ε-γ]-Glu-[α-γ]-Glu)-Arg-Gln-Gln-COOH (SEQ ID NO:
- 12).
A method for selectively destroying a target cell that is a cancer cell, comprising contacting the target cell with a procytotoxin, which comprises a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue, wherein said peptide without said modification is a cytotoxic peptide, and wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and the procytotoxin comprises the structure N-Gly-Phe-Ile-Ala-Thr-Leu-Cys-Thr-Lys-Val-Leu-Asp-Phe-Gly-Ile-Asp-Lys-Leu-Ile-Gln-Leu-Ile-Glu-Asp-Lys([ε-γ]-Glu-[α-γ]-Glu)-CONH2 (SEQ ID NO. 8).
A procytotoxin comprising a peptide comprising at least one lysine residue bound via a peptide bond to at least one amino acid via the ε-amino group of said lysine residue,
- (i) wherein said peptide without the modification is a pore-forming cytolytic peptide,
- (ii) wherein said at least one amino acid bound via the ε-amino group of said lysine residue acts to prevent the peptide from forming a lytically active conformation, and
- (iii) wherein said cytolytic peptide need not be internalized to cause target-specific cell death.
Dependencies are inferred from the claim text.