Compounds for stimulating P-glycoprotein function and uses thereof
The present invention is directed to polypeptides (e.g., fragments) derived from P-glycoprotein and caveolin-1 which are capable of inhibiting the interaction between these two proteins. Inhibition of this interaction leads to increase of efflux of compounds that are transported by P-gp. The invention further includes methods of treating patients having diseases that benefit from increased P-gp-mediated efflux. Such diseases include neoplasms such as cancer and neurological diseases such as neurodegenerative diseases.
1. A soluble polypeptide comprising the amino acid sequence VFSMFRYSNWLDK (SEQ ID NO: 3), wherein said polypeptide
is less than 1000 amino acids in length and
specifically binds caveolin-1.
2. The polypeptide of claim 1 consisting of the amino acid sequence VFSMFRYSNWLDK (SEQ ID NO:3).
3. A method of increasing P-gp-mediated efflux in a cell, said method comprising administering a polypeptide of claim 1 in an amount sufficient to increase P-gp-mediated efflux.
4. A fusion protein comprising:
(a) a soluble polypeptide comprising the amino acid sequence VFSMFRYSNWLDK (SEQ ID NO:3), wherein said polypeptide is less than 1000 amino acids in length and specifically binds caveolin-1, and
(b) a heterologous sequence.