Molecular guide system peptides and uses thereof
Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.
1. A composition comprising an antibody conjugated to a molecular guidance system (MGS) peptide, directly or via a linker, wherein the MGS peptide is selected from the group consisting of:
YAAWPASGAWT (SEQ ID NO: 6), D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), KQYATPRVFWT (SEQ ID NO: 33), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL -PEG 11 -C-NH 2 (SEQ ID NO: 72), CH 3 CO-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 73), CH 3 CO-D-Leu-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 74), CH 3 CO-FHAVPQSFYT (SEQ ID NO: 80), CH 3 CO-D-Leu-RGDLATLRQL (SEQ ID NO: 81), CH3CO -YAAWPASGAWT (SEQ ID NO: 82), CH 3 CO-KQYATPRVFWT (SEQ ID NO: 84), and CH 3 CO-LQWRRNFGVWARYRL (SEQ ID NO: 85).
2. The composition of claim 1 , wherein the antibody targets an intracellular target, and wherein the MGS peptide is selected from the group consisting of:
YAAWPASGAWT (SEQ ID NO: 6), D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), KQYATPRVFWT (SEQ ID NO: 33), CH 3 CO -YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL -PEG 11 -C-NH 2 (SEQ ID NO: 72), CH 3 CO-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 73), CH 3 CO-D-Leu-RGDLATLRQL-PEG 11 -YC-NH 2 (SEQ ID NO: 74), CH 3 CO-FHAVPQSFYT (SEQ ID NO: 80), CH 3 CO-D-Leu-RGDLATLRQL (SEQ ID NO: 81), CH3CO-YAAWPASGAWT (SEQ ID NO: 82) and CH 3 CO-KQYATPRVFWT (SEQ ID NO: 84).
3. The composition of claim 1 , wherein the antibody is a monoclonal antibody.
4. The composition of claim 3 , wherein the monoclonal antibody is an anti-Ras monoclonal antibody.
5. The composition of claim 1 , wherein the antibody is conjugated to the MGS peptide via a linker.
6. The composition of claim 1 , wherein the antibody is conjugated to the MGS peptide as a fusion protein.
7. A method of targeting an intracellular target in a cell in vitro or in a subject, comprising contacting the cell with or administering to the subject a composition according to claim 1 , wherein the antibody targets an intracellular target.
8. The method of claim 7 , wherein the method comprises administering, to the subject having a disease in need thereof, an effective amount of the composition, and wherein the antibody targets the intracellular target involved in the disease process.
9. The method of claim 8 , wherein the subject in need thereof has an infectious disease, cancer, diabetes, a neurological or neurodegenerative disease, a genetically-inherited disease, or has been exposed to a bioterrorism agent.
10. The method of claim 7 , wherein the linker comprises polyethylene glycol (PEG).
11. A molecular guidance system (MGS) peptide selected from the group consisting of:
D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), CH 3 CO-LQWRRNFGVWARYRL-PEG 11 -C-NH 2 (SEQ ID NO: 72), and CH 3 CO-LQWRRNFGVWARYRL (SEQ ID NO: 85).
12. The MGS peptide of claim 11 , wherein the MGS peptide is conjugated to an antibody, directly or through a linker.
13. The MGS peptide of claim 12 , wherein the linker comprises polyethylene glycol (PEG).
14. The MGS peptide of claim 11 , wherein the MGS peptide is selected from the group consisting of:
D-Leu-RGDLATLRQL (SEQ ID NO: 8), LQWRRNFGVWARYRL (SEQ ID NO: 31), CH 3 CO-YAAWPASGAWT-PEG 11 -C-NH 2 (SEQ ID NO: 71), and CH 3 CO-LQWRRNFGVWARYRL-PEG 11 -C-NH 2 (SEQ ID NO: 72).