Combined preparation of a thiazide diuretic and a loop diuretic
The specific molecular basis of the interaction between talin and integrin β 3 has been defined. This specific interaction provides a new therapeutic target; agents that can disrupt this specific interaction should be useful therapeutic agents for a number of significant diseases and conditions including inflammation, heart disease, including myocardial infarction, and tumor metastasis. The present invention includes a chimeric peptide that has high affinity for talin, muteins of talin and integrin β 3 as well as screening methods for agents that can disrupt the interaction between talin and integrin β 3 .
1. A chimeric peptide comprising:
(a) a tryptophan (W) residue that binds to a pocket on the surface of talin molecule;
(b) a membrane proximal (MP) peptide of β 3 integrin tail comprising the amino acid sequence KLLITIHDRKEFAKFEEERARAK (SEQ ID NO: 7), wherein at least one F residue is mutated, on the aminoterminal side of the tryptophan residue of (a); and
(c) a C-terminal peptide PIPKIγ comprising the amino acid sequence VpYSPLHYSAR (SEQ ID NO: 8) on the carboxyl-terminal side of the tryptophan residue of (a) to form a binding site in conjunction with (a) and (b); wherein the chimeric peptide is soluble and has higher affinity for talin than β 3 integrin tail.
2. The chimeric peptide of claim 1 , wherein at least one F residue in SEQ ID NO:7 is mutated with A residue.
3. The chimeric peptide of claim 1 , wherein both F residues in SEQ ID NO:7 are mutated with A residues.
4. The chimeric peptide of claim 1 , wherein said C-terminal peptide of PIPKIγ is the amino acid sequence VpYSPLHYSAR (SEQ ID NO: 8).
5. The chimeric peptide of claim 1 , wherein said chimeric peptide is expressed by a host cell transformed or transfected with a nucleotide encoding said chimeric peptide.
6. The chimeric peptide of claim 1 , wherein said chimeric peptide is chemically synthesized.