Autophagy-inducing peptide
View Patent ↗An autophagy-inducing compound comprises an autophagy-inducing peptide comprising beclin-1 residues 269-283 and a heterologous moiety that promotes therapeutic stability or delivery of the compound. The compound may be used to induce autophagy and in assays with beclin-1 binding partners.
1. An autophagy-inducing compound comprising (a) an autophagy-inducing peptide comprising Beclin 1 residues 269-283 (SEQ ID NO:1) immediately flanked on each terminus by no more than 12 naturally-flanking Beclin 1 residues, wherein up to six of said residues 269-283 may be substituted, and (b) a first heterologous moiety that is heterologous to the peptide.
2. The compound of claim 1 , wherein the peptide is N-terminally flanked with T-N and C-terminally flanked by T.
3. The compound of claim 1 , wherein the peptide comprises at least one of F270, F274 and W277.
4. The compound of claim 1 , wherein the peptide comprises at least one of substitutions: H275E, S279D and Q281E.
5. The compound of claim 1 , wherein the peptide is N-terminally joined to the first moiety, and C-terminally joined to a second heterologous moiety.
6. The compound of claim 1 , wherein the peptide is joined to the first moiety through a linker.
7. The compound of claim 1 , wherein the first moiety comprises a transduction domain.
8. The compound of claim 1 , wherein the first moiety comprises homing peptide.
9. The compound of claim 1 , wherein the first moiety comprises a serum stabilizing agent.
10. The compound of claim 1 , wherein the peptide comprises one or more D-amino acids, L-β-homo amino acids, D-β-homo amino acids, or N-methylated amino acids.
11. The compound of claim 1 wherein the peptide is cyclized.
12. The compound of claim 1 comprising an N-terminal acetyl, formyl, myristoyl, palmitoyl, carboxyl or 2-furosyl group, and/or a C-terminal hydroxyl, amide, ester or thioester group.
13. The compound of claim 1 wherein the peptide is acetylated, acylated, formylated, amidated, phosphorylated, sulfated or glycosylated.
14. The compound of claim 1 comprising an affinity tag or detectable label.
15. The compound of claim 1 , wherein the peptide is N-terminally joined to the first moiety, and C-terminally joined to a second heterologous moiety comprising a fluorescent label.
16. The compound of claim 1 , wherein the peptide is N-terminally flanked with T-N and C-terminally flanked by T, and the first moiety is a tat protein transduction domain linked to the peptide through a diglycine linker.
17. The compound of claim 1 , wherein the peptide is N-terminally flanked with T-N and C-terminally flanked by T, and the first moiety is a tetrameric integrin α(v)β(6)-binding peptide known as H2009.1, linked to the peptide through a maleimide-PEG(3) linker.
18. A method of inducing autophagy, comprising administering to a person in need thereof an effective amount of a composition of claim 1 .