Tight junction protein modulators and uses thereof

Abstract

The invention provides tight junction protein modulators, compositions comprising the same, and uses thereof. In particular, the invention provides tight junction protein modulators that modulate the second extracellular loop of tight junction proteins, such as occludin or claudin.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is Continuation-In-Part Application of U.S. patent application Ser. No. 12 / 743,816, filed May 19, 2010, which is a U.S. national phase application of PCT Patent Application No. PCT / US08 / 84100, filed Nov. 19, 2008, which claims the priority benefit of U.S. Provisional Application No. 60 / 988,865, filed Nov. 19, 2007, all of which are incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY FUNDED RESEARCH[0002]This invention was made with government support under grant number DOD DAMD17-00-1-0210 awarded by the Department of Defense and grant number PO1-HD38129 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]The invention relates to tight junction protein modulators, compositions comprising the same, and uses thereof. In particular, the invention relates to peptide modulators of tight junction proteins that mimic or modulate...

AI Technical Summary

Benefits of technology

[0031]Other aspects of the invention provide methods for removing at least a portion of epithelia cells from a subject. Generally such methods include causing apoptosis of the epithelia cells; however, it should be appreciated that methods can also simply involve disrupting the tight junction protein to cause removal of adhesion between epithelial cells. Such methods typically comprise administering to the subject in need of such treatment a tight junction protein inhibitor. In some embodiments, the epithelia cells are in hyperplastic stages. In one particular instance, the epithelia cells are in the subject's breast. In such instance, the tight junction protein can be administered to the subject by intraductal injection.

[0032]Still other aspects of the invention provide a compound comprising 20 (typically 10, often 6) amino acid sequences or less and at least 3 consecutive amino acid sequences of the second extracellular loop sequence of occludin or claudin, or a derivative thereof. In some embodiments, the compound comprises amino acid sequences of LYHY, ZFYNP, or a derivative or a combination thereof.

Problems solved by technology

Tight junction disruption induces epithelial to mesenchymal transition, increases cellular motility, produces overgrowth of cultured cells, and increases tumorigenicity of cells transplanted into animals.

Although tight junction protein modulators are known, these are not without any problems.

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