Peptides whose uptake by cells is controllable
A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
1. A method for labeling a cell, comprising contacting the cell with a molecule comprising the structure
A-X-B-C (Formula I),
wherein
C is a fluorescent moiety,
B is a peptide sequence comprising a series of 8 D-arginine residues,
A is a peptide sequence comprising a series of 5 glutamate residues, and
X is a cleavable linker.
2. The method of claim 1 , wherein X is a pH-sensitive linker.
3. The method of claim 1 , wherein X is cleaved in the extracellular space.
4. The method of claim 1 , wherein X is cleaved by a protease, a matrix metalloproteinase, or a combination thereof.
5. The method of claim 1 , further comprising a fluorescent quenching moiety attached to A.
6. The method of claim 1 , wherein the fluorescent moiety is a fluorescent cyanine.