Chlorotoxin polypeptides and conjugates and uses thereof

A modified chlorotoxin peptide having a single lysine residue.

A chlorotoxin polypeptide, wherein the chlorotoxin polypeptide has at least 90% sequence identity with SEQ ID NO:

• 1, and wherein each lysine residue present in the chlorotoxin polypeptide, except for the lysine residue corresponding to position 27 of SEQ ID NO:1, is blocked from participating in a chemical conjugation reaction by a modification to the lysine residue.

A method comprising a step of:

• administering to a subject having or suspected of having a tumor an effective amount of the pharmaceutical composition comprising a chlorotoxin polypeptide associated with at least one therapeutic moiety, at least one detectable moiety, or combination thereof, wherein the chlorotoxin polypeptide has at least 90% sequence identity with SEQ ID NO:
• 1, and wherein each lysine residue present in the chlorotoxin polypeptide, except for the lysine residue corresponding to position 27 of SEQ ID NO:1, is blocked from participating in a chemical conjugation reaction by a modification to the lysine residue, such that the chlorotoxin polypeptide binds specifically to the tumor in the subject.

A chlorotoxin polypeptide having one lysine available as a site for conjugation, wherein the lysine is at a position corresponding to position 15 of SEQ ID NO:

• 1.

A chlorotoxin polypeptide having one lysine available as a site for conjugation, wherein the lysine is at a position corresponding to position 23 of SEQ ID NO:

• 1.

A chlorotoxin polypeptide having one lysine available as a site for conjugation, wherein the lysine is at a position corresponding to position 27 of SEQ ID NO:

• 1.

A chlorotoxin polypeptide having no lysine residues.

A method for treating a disease or condition treatable by administering chlorotoxin, comprising administering an effective amount of a modified chlorotoxin peptide having a single lysine residue to a subject in need thereof.

A method for detecting cancer detectable by chlorotoxin, comprising contacting a tissue with a modified chlorotoxin peptide covalently coupled to one or more of a therapeutic, diagnostic, imaging, or targeting agent, or a moiety that increases the circulatory half-life of the modified chlorotoxin peptide, and having a single lysine residue, to detect cancer detectable by chlorotoxin.