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. Cleavage of X allows
separation of A from B, unmasking the normal ability of the basic amino
acids in B to drag cargo C into cells near the cleavage event. X is
cleaved extracellularly, preferably under physiological conditions.
D-amino acids are preferred for the A and B portions, to minimize
immunogenicity and nonspecific cleavage by background peptidases or
proteases.