Retroinverso polypeptides that mimic or inhibit thrombospondin
AssigneeInkine Pharmaceuticals Mcp Hahnemann
InventorsTaffy Williams, George Tuszynski, Paul Actor
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Abstract
The present invention relates generally to polypeptides that mimic or inhibit the biological activity of thrombospondin, and particularly to polypeptides in retroinverso form. The peptides. These polypeptides may be used biological and pharmaceutical applications such as: (a) inhibiting the invasive and metastatic activity of melanoma cells, (b) promoting and inhibiting cellular attachment to tissue culture flasks, (c) promoting wound healing, angiogenesis, and implant acceptance, (d) agents for anti-platelet aggregation, (e) agents for antimalarial activity, and (f) diagnostic reagents in different therapeutic applications, as well as other related areas.
Claims14
A polypeptide having the retroinverso form of a polypeptide of formula (I)
- Z1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Z2 (SEQ ID NO:
- ______)
- wherein:
- Xaa2 is a neutral/non-polar/large/cyclic amino acid residue;
- Xaa3 is a neutral/polar/small or neutral/polar/large/non-cyclic or acidic amino acid residue;
- Xaa4 is a neutral/nonpolar/large/cyclic or neutral/non-polar/large/non-cyclic or neutral/polar/large/non-cyclic or neutral/polar/small amino acid residue;
- Xaa5 is a neutral/polar/small amino acid residue
- Xaa6 is a neutral/polar/small or neutral/polar/large/non-cyclic amino acid residue;
- Xaa7 is a neutral/nonpolar/large/non-cyclic or neutral/polar/large/non-cyclic amino acid residue;
- Xaa8 is a neutral/polar/large/non-cyclic or neutral/polar/small amino acid residue;
- Xaa9 is a neutral/polar/small amino acid residue;
- Xaa10 is a neutral/polar/small amino acid residue;
- Z1 is hydrogen, amino, acetyl or at least one amino acid residue or the desamino form thereof;
- Z2 is hydroxyl, carboxyl, non-amino acids such as agmatine, or at least one amino acid residue, including carboxyamide or alkylamide forms thereof;
- and
- wherein said polypeptide mimics or inhibits the biological activity of thrombospondin.
A polypeptide having the retroinverso form of a polypeptide of formula (II):
- R1-Cys-Xaa11-Xaa12-Xaa13-Cys-R2 (SEQ ID NO:
- ______)
- wherein:
- R1 is a protected or unprotected terminal amino group, including hydrogen, amino, acetyl or at least one amino acid residue or the desamino form thereof;
- Xaa11, Xaa12, and Xaa13 are the same or different neutral/non-polar/large/non-cyclic or neutral/polar/large/non-cyclic or neutral/polar/small or basic/non-cyclic amino acid residues, preferably selected from the group consisting of valine, threonine, serine, and arginine;
- R2 is a protected or unprotected terminal carboxyl group including hydroxyl, carboxyl, or at least one amino acid residue, including carboxyamide or alkylamide forms thereof, preferably selected from the group consisting of lysine, glycine, and arginine;
- wherein the structure of the polypeptide is optionally cyclized through a bond between the cysteines, such as a disulfide bond, or a bond between R1 and R2;
- and wherein said polypeptide mimics or inhibits the biological activity of thrombospondin.
A retroinverso polypeptide having the formula d-Gly-Cys-Thr-Val-Ser-Cys (SEQ ID NO:
- ______), wherein the cysteine residues are modified with a sulfhydral blocking group.
Dependencies are inferred from the claim text.