Activatable therapeutic peptides and uses thereof
AssigneeMassachusetts Institute of Technology
InventorsSangeeta N. Bhatia, Chayanon Ngambenjawong
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Abstract
Disclosed herein are fusion protein, comprising (a) at least one X1 domain comprising a half-life extension compound, including but not limited to a half-life extension polypeptide; (b) at least one X2 domain comprising an anionic block; (c) at least one X3 domain comprising a linker susceptible to cleavage at a site of disease, including but not limited to a microbial infection site or tumor site; and (d) at least one X4 domain comprising a therapeutic peptide; wherein the at least one X1, X2, X3, and X4 domains are covalently linked, and each X4 domain is linked to an X3 domain without an intervening X1 or X2 domain; compositions containing such fusion proteins, and methods for their use.
Claims10
A fusion protein, comprising:
- (a) at least one X1 domain comprising a to a half-life extension polypeptide, wherein each X1 domain comprises the amino acid sequence (MG) LKEAKEKA IEELKKAGIT SDYYFDLINK AKTVEGVNAL KDEILKA (SEQ ID NO:
- 4), wherein the residues in parentheses are optional and may be present or absent, or wherein each X1 domain independently comprises the amino acid sequence LKEAKEKA IEELKKAGIT SDYYFDLINK AKTVEGVNAL KDEILKA (SEQ ID NO:
- 5);
- (b) at least one X2 domain comprising an anionic block, wherein each X2 domain comprises the amino acid sequence (EEG) x, wherein “x” is 1-20, 2-16, 3-12, 4-10, 5-8, 1-15, 1-10, 2-10, 3-10, 4-10, 5-10, 2-8, 3-8, 4-8, 5-8, 5-7, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
- (c) at least one X3 domain comprising a linker susceptible to cleavage at a site of disease, wherein each X3 domain comprises the amino acid sequence PLGLRSW (SEQ ID NO:
- 16);
- and
- (d) at least one X4 domain comprising a therapeutic peptide, wherein each X4 domain comprises the amino acid sequence GiGkflkkakkfGkafvkilkk (SEQ ID NO:
- 137);
- and/or GiGkflkkakkfGkafvkilkkK (SEQ ID NO:
- 138);
- and/or Cyclo-(T-W-I-(Dab)-(Orn)-(Dab)-(Dab)-W-(Dab)-(Dab)-A-S-p-P) (SEQ ID NO:
- 139);
- and/or 6-methyloctanoic acid-Dab-T-Dab-(Dab-Dab-1-L-Dab-Dab-T) (SEQ ID NO:
- 140), wherein residues in lower case are D amino acids and residues in upper case are L amino acids or glycine, and Dab and Orn denote L-diaminobutyric acid and L-ornithine respectively;
- wherein the at least one X1, X2, X3, and X4 domains are covalently linked, and each X4 domain is linked to an X3 domain without an intervening X1 or X2 domain.
Dependencies are inferred from the claim text.