Compounds having RD targeting motifs
The present invention provides compounds that have motifs that target the compounds to cells that express integrins. In particular, the compounds have peptides with one or more RD motifs conjugated to an agent selected from an imaging agent and a targeting agent. The compounds may be used to detect, monitor and treat a variety of disorders mediated by integrins.
1. A compound having the formula:
R 1 -[GRDSPK] n -R 2
wherein:
R 1 and R 2 are independently selected from the group consisting of an imaging agent, a treatment agent, hydrogen, hydroxyl, hydrocarbyl, and substituted hydrocarbyl, provided at least one of R 1 or R 2 is an imaging agent or a treatment agent;
GRDSPK (SEQ ID NO:8) is a linear or cyclic peptide;
n is an integer from 1 to about 10; and
a dash (-) represents a covalent bond.
2. The compound of claim 1 , wherein one of R 1 or R 2 is an imaging agent selected from the group consisting of a fluorescent dye, a fluorescent semiconductor particle, paramagnetic or superparamagnetic material, and a radioisotope.
3. The compound of claim 1 , wherein one of R 1 or R 2 is a treatment agent selected from the group consisting of a drug and a hormone.
4. The compound of claim 1 , further comprising a linker, L 1 , that conjugates R 1 to X 1 .
5. The compound of claim 1 , further comprising a linker, L 2 , that conjugates R 2 to X 2 .
6. The compound of claim 1 , wherein n is from 1 to 5.
7. A compound having the formula:
R 1 -[X 1 m —R-D-X 2 p ] n —R 2 (SEQ ID NO:55)
wherein:
R 1 and R 2 are independently selected from the group consisting of a carbocyanine dye, a treatment agent, hydrogen, hydroxyl, hydrocarbyl, and substituted hydrocarbyl, provided at least one of R 1 or R 2 is a carbocyanine dye;
X 1 m —R-D-X 2 p together form a linear or cyclic peptide;
each X 1 and each X 2 are independently selected from the group consisting of G, S, N, Q, D, E, K, R, T, Y, C, H, and P;
m is an integer from 1 to about 10;
n is an integer from 1 to about 10;
p is an integer from 1 to about 10; and
a dash (-) represents a covalent bond.
8. The compound of claim 7 , wherein one of R 1 or R 2 is a treatment agent selected from the group consisting of a drug and a hormone.
9. The compound of claim 7 , further comprising a linker, L 1 , that conjugates R 1 to X 1 .
10. The compound of claim 7 , further comprising a linker, L 2 , that conjugates R 2 to X 2 .
11. The compound of claim 7 , wherein:
n is from 1 to 5;
m is from 1 to 3; and
p is from 1 to 3.
12. The compound of claim 7 , further comprising at least one cyclic peptide having a RGD motif.
13. The compound of claim 12 , wherein the cyclic peptide has from about 4 amino acid residues to about 10 amino acid residues.
14. The compound of claim 7 , wherein the carbocyanine dye is cypate.
15. A method for detecting expression of a β 3 subunit of integrin in a cell, the method comprising:
(a) contacting a population of cells with a compound of claim 7 ; and
(b) detecting the presence of a signal emitted from the carbocyanine dye of the compound of claim 7 in the population of cells, the signal being emitted from a cell expressing a β 3 subunit of integrin.