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Title: 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. 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.
Inventors:
;
Issue Date:
OSTI Identifier:
1118269
Assignee:
The Regents of the University of California (Oakland, CA) OAK
Patent Number(s):
8,642,561
Application Number:
13/314,134
Contract Number:
FG03-01ER63276
Resource Relation:
Patent File Date: 2011 Dec 07
Research Org:
The Regents of the University of California, Oakland, CA, USA
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Other works cited in this record:

Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring
journal, October 1999

Tumor imaging by means of proteolytic activation of cell-penetrating peptides
journal, December 2004
  • Jiang, T.; Olson, E. S.; Nguyen, Q. T.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 51, p. 17867-17872
  • DOI: 10.1073/pnas.0408191101

Arginine containing peptides as delivery vectors
journal, February 2003

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters
journal, November 2000
  • Wender, P. A.; Mitchell, D. J.; Pattabiraman, K.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 24, p. 13003-13008
  • DOI: 10.1073/pnas.97.24.13003

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