RECEPTOR-MEDIATED UPTAKE OF PEPTIDES THAT BIND THE HUMAN TRANSFERRIN RECEPTOR
Peptides have been discovered which are capable of binding to and internalizing with the human transferrin receptor (hTfR). The sequences HAIYPRH (Seq. ID No. 1) and THRPPMWSPVWP (Seq. ID No. 2) are capable of binding to and internalizing with the human transferrin receptor. When these molecules were fused with other molecules, the fusion product was internalized in cells expressing hTfR. The sequences have use for targeting other peptides and proteins into cells expressing hTfR.
1 . A method of targeting an agent to a transferrin receptor in a subject, said method comprising the step of administering to the subject a peptide containing the sequence HAIYPRH (SEQ. ID NO: 1) linked to the agent.
2 . The method of claim 1 where the transferrin receptor is a human transferrin receptor.
3 . The method of claim 1 where the agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
4 . The method of claim 3 where the chemotherapeutic agent or antineoplastic agent is cisplatin, a nitrogen mustard, such as but not limited to, chlorambucil, an ethylenimine, a methylmelamine, a nitrosourea, such as but not limited to, carmustine or lomustine, doxorubicin or methotrexate.
5 . The method of claim 1 where the agent is a liposome.
6 . The method of claim 5 where the liposome contains a second agent.
7 . The method of claim 6 where the second agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
8 . The method of claim 1 where the binding of the peptide containing the sequence HAIYPRH (SEQ ID NO: 1) linked to the agent does not completely prevent transferrin from binding the transferring receptor.
9 . A method of targeting an agent to a transferrin receptor in a subject, said method comprising the step of administering to the subject a peptide linked to the agent, wherein the peptide binds to the transferrin receptor at a site distinct from a site where transferrin binds the transferrin receptor.
10 . The method of claim 9 where the peptide contains the sequence HAIYPRH (SEQ ID NO: 1) or THRPPMWSPVWP (SEQ ID NO: 2).
11 . The method of claim 9 where the transferrin receptor is a human transferrin receptor.
12 . The method of claim 9 where the agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
13 . The method of claim 12 where the chemotherapeutic agent or antineoplastic agent is cisplatin, a nitrogen mustard, such as but not limited to, chlorambucil, an ethylenimine, a methylmelamine, a nitrosourea, such as but not limited to, carmustine or lomustine, doxorubicin or methotrexate.
14 . The method of claim 9 where the agent is a liposome.
15 . The method of claim 14 where the liposome contains a second agent.
16 . The method of claim 15 where the second agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
17 . A method of treating a subject in need thereof, the method comprising the step of administering to the subject a peptide linked to an agent, wherein the peptide contains the sequence HAIYPRH (SEQ. ID NO: 1) or THRPPMWSPVWP (SEQ ID NO: 2) and targets the agent to a cell expressing a transferrin receptor.
18 . The method of claim 17 where the transferrin receptor is a human transferrin receptor.
19 . The method of claim 17 where the agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
20 . The method of claim 19 where the chemotherapeutic agent or antineoplastic agent is cisplatin, a nitrogen mustard, such as but not limited to, chlorambucil, an ethylenimine, a methylmelamine, a nitrosourea, such as but not limited to, carmustine or lomustine, doxorubicin or methotrexate.
21 . The method of claim 17 where the agent is a liposome.
22 . The method of claim 21 where the liposome contains a second agent.
23 . The method of claim 22 where the second agent is a peptide, a protein, an antigen, a chemotherapeutic agent, an antineoplastic agent, an imaging agent or a radioisotope.
24 . The method of claim 17 where the cell expressing the transferrin receptor is a cancerous cell and the agent is a therapeutic agent or a diagnostic agent.
25 . The method of claim 22 where the cell expressing the transferrin receptor is a cancerous cell and the agent is a therapeutic agent or a diagnostic agent.