Targeted pharmacological chaperones

1. A method of treating a lysosomal storage disease in a subject, comprising:

A. preparing a targeted pharmacological chaperone having a formula selected from the group consisting of:

and

B. administering a therapeutically effective amount of said targeted pharmacological chaperone to a subject suffering from a disease caused by a defective protein.

2. The method of claim 1 , wherein said targeted pharmacological chaperone further comprises one or more substituents selected from the group consisting of an unsubstituted carboxylic acid ester and an alkyloxy substituted carboxylic acid ester.

3. The method of claim 2 , wherein said substituent is selected from the group consisting of an acetoxymethyl (AM) ester and an acetate ester.

4. A method as in claim 1 , wherein the targeted pharmacological chaperone or chaperones are administered to the subject undergoing enzyme replacement therapy (ERT) for the disease, wherein the targeted pharmacological chaperone acts to deliver the enzyme into the cells and partition it into specific organelles within the diseased patient cells.

5. A composition having the general formula:

T-LINK-DRUG

where T represents a targeting group that is a peptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, and SEQ ID NO:25;

where DRUG represents a small molecule compound selected from the group consisting of deoxynojirimycin, deoxygalactonojirimycin, N-butyldeoxynojirimycin, N-alkylgalactonojirimycin, N-butyldeoxymannonojirimycin, N-alkyl-deoxymannonojirimycin, N-butyl-2-deoxy-2-N-acetylnojirimycin, N-alkyl-2-deoxy-2-N-acetylnojirimycin, 1-deoxygalactonojirimycin N-butylmaleimide, 1-deoxymannonojirimycin N-butylmaleimide, 1-deoxynojirimycin N-ethylmaleimide, D-Glucosamine N-butylmaleimide, 1-thio-deoxyglucose, p-carboxyphenethyl-1-thio-1-deoxy-glucose, and 2-[4-(5-carboxypentyl)phenyl]ethyl-1-deoxy-1-thio-β-D-glucopyranoside, and N-(4′-maleimidobutyl)-1-deoxynojirimycin; and

where LINK represents an optional linking group having 1-20 non-hydrogen atoms selected from the group consisting of C, N, O and S composed of any combination of chemical bonds, including ether, thioether, succinylthioether, benzylthioether, amine, ester, carboxamide, sulfonamide, hydrazide bonds, and single, double, triple carbon-carbon bonds, and aromatic or heteroaromatic bonds.

6. The composition of claim 5 , wherein the LINK groups are composed of any combination of single carbon-carbon bonds and carbon-sulfur bonds including methylenes, oligomethylenes, phenylenes, thienyls, carboxamides, and sulfonamides.

7. The composition of claim 5 , wherein LINK contains 1-6 carbon atoms and has the formula —(CH 2 ) a (N(COCH 2 ) z —, where a has any value from 0-5 and z is 1 or 2.

8. The composition of claim 5 , wherein LINK has the formula —(CH 2 ) a (N(COPCH 2 ) z —, where a has any value from 0-5.

9. The composition of claim 5 , wherein the LINK contains a reactive group selected from the group consisting of carboxyl, maleimide, benzylchloromethyl, iodoacetamide or a peptide reactive functionality for attachment of LINK to the Targeting Group T.

10. The composition of claim 5 , wherein said composition further comprises one or more substituents selected from the group consisting of an unsubstituted carboxylic acid ester and an alkyloxy substituted carboxylic acid ester.

11. The composition of claim 10 , wherein said substituent is selected from the group consisting of an acetoxymethyl (AM) ester and an acetate ester.

12. The composition of claim 5 , wherein said composition has a formula selected from the group consisting of:

A.

where R1, R2, R3 and R4 are independently selected from the group consisting of H and OH, and

where peptide comprises an amino acid having a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, and SEQ ID NO:25;

B.

where R1 and R2 are independently selected from the group consisting of H and OH, and

where peptide comprises an amino acid having a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, and SEQ ID NO:25; and

C.

where R1 and R2 are independently selected from the group consisting of H and OH, and where peptide comprises an amino acid having a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, and SEQ ID NO:25.

13. A composition having a formula selected from the group consisting of: