KIF13B-derived peptide and method of inhibiting angiogenesis
View Patent ↗A construct composed of a Kinesin-derived Angiogenesis Inhibitor peptide and one or more carrier moieties and/or stabilizing moieties is provided as are methods for inhibiting angiogenesis and treating a disease or condition characterized by excessive vascularity.
1. A construct of no more than 65 amino acids comprising the amino acid sequence Thr-Pro-Xaa 1 -Asp-Glu-Arg-Xaa 2 -Xaa 3 -Leu-Ile-Xaa 4 -Arg-Val-Xaa 5 -Val-Xaa 6 (SEQ ID NO:2) operably linked to
(a) one or more carrier moieties,
(b) one or more stabilizing moieties, or
(c) a combination of (a) and (b),
wherein Xaa 1 is Val, Ala or Ser; Xaa 2 is Leu or Val; Xaa 3 is Phe or Tyr; Xaa 4 is Leu or Val; Xaa 5 is Thr or Ala; and Xaa 6 is Gln or Arg.
2. The construct of claim 1 , wherein the one or more carrier moieties comprise a cell penetrating peptide, a lipid, Vitamin 12 , or a combination thereof.
3. The construct of claim 2 , wherein the cell penetrating peptide comprises a peptide of SEQ ID NO:4-60.
4. The construct of claim 1 , wherein the one or more stabilizing moieties comprise a peptide, post-translational modification, non-natural amino acid residue, a macromolecule or a combination thereof.
5. The construct of claim 4 , wherein the post-translational modification comprises N-terminal acetylation or C-terminal amidation.
6. The construct of claim 4 , wherein the non-natural amino acid residue comprises a D-amino acid residue.
7. The construct of claim 4 , wherein the macromolecule comprises polyethylene glycol, polysialic acid, hydroxyethyl starch, albumin or an immunoglobulin fragment.
8. The construct of claim 1 , wherein said construct comprises the amino acid sequence TPVDERLFLIVRVTVQ (SEQ ID NO:3).
9. The construct of claim 8 , wherein said construct is SRGTPVDERLFLIVRVTVQLSHP-NH 2 (SEQ ID NO:113).
10. A pharmaceutical composition comprising the construct of claim 1 and a pharmaceutically acceptable excipient.
11. A method for inhibiting angiogenesis comprising contacting cells or tissue with an effective amount of a construct of claim 1 thereby inhibiting angiogenesis in the cells or tissue.
12. A method of treating a disease or condition in a subject characterized by excessive vascularity comprising administering to the subject an effective amount of a construct of claim 1 thereby treating the disease or condition.
13. The method of claim 12 , wherein the disease or condition is an inflammatory disease, cancer, or retinal vasculopathy.