Peptides whose uptake by cells is controllable

Details Peptides whose uptake by cells is controllable Peptides whose uptake by cells is controllable

2003-10-31

2008-10-07

Jones, D. L (Department: 1618)

Drug, bio-affecting and body treating compositions

Radionuclide or intended radionuclide containing; adjuvant...

In an organic compound

C424S001110, C424S001650, C530S300000

Reexamination Certificate

active

07431915

ABSTRACT:
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.

REFERENCES:
patent: 4507389 (1985-03-01), Weingarten
patent: 2005/0107583 (2005-05-01), Jiang et al.
Golub et al., Science, Oct. 15, 1999, pp. 531-537.
Ullrich, K.J., et al. “Controluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney”,Pflügers Arch(1989) 415:342-350.

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