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Peptides whose uptake by cells is controllable

United States Patent

February 4, 2014
View the Complete Patent at the US Patent & Trademark Office
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.
Jiang; Tao (San Diego, CA), Tsien; Roger Y. (La Jolla, CA)
The Regents of the University of California (Oakland, CA)
13/ 314,134
December 7, 2011
STATEMENT OF FEDERALLY-SPONSORED RESEARCH This invention was made with government support under NS27177 awarded by National Institute of Health, under W81XWH-05-1-0183 awarded by the Army, and under DE-FG-03-01ER63276, awarded by Department of Energy. The government has certain rights in this invention.