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Title: Peptides whose uptake by cells is controllable

Patent ·
OSTI ID:1037757

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.

Research Organization:
University of California (Oakland, CA)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG03-01ER63276
Assignee:
The Regents of the University of California (Oakland, CA)
Patent Number(s):
8,110,554
Application Number:
12/244,602
OSTI ID:
1037757
Country of Publication:
United States
Language:
English

References (7)

Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation journal November 2000
Arginine-Rich Molecular Transporters for Drug Delivery:  Role of Backbone Spacing in Cellular Uptake journal August 2002
Tumor imaging by means of proteolytic activation of cell-penetrating peptides journal December 2004
Contraluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney: VI. Specificity: Amino acids, their N-methyl-, N-acetyl- and N-benzoylderivatives; glutathione- and cysteine conjugates, di- and oligopeptides journal December 1989
Macrocyclic Chelators with Paramagnetic Cations Are Internalized into Mammalian Cells via a HIV-Tat Derived Membrane Translocation Peptide journal May 2000
Visualizing the mechanical activation of Src journal April 2005
The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters journal November 2000

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