TARGETED PHARMACOLOGICAL CHAPERONES

摘要

The present invention relates to the preparation and use of therapeutic compounds for the treatment of diseases at specific subcellular target areas such as specific cellular organelles. In particular, the therapeutic compounds of the invention are specific for modifying enzyme activity within targeted organelles or structures of cells and tissues. Subcellular organelles and structures that may be specifically targeted by compounds of the present invention include lysosomes, autophagasomes, the endoplasmic reticulum, the Golgi complex, peroxisomes, the nucleus, membranes and the mitochondria.

主权项

1. A method of treating disease caused by a defective protein in a subject, comprising:
A. preparing a targeted pharmacological chaperone having the general formula:
T(R)-LINK-DRUG(R); where T represents a targeting group that is a peptide that partitions the pharmacological chaperone for specific import to or retention in particular organelles within the cell; where DRUG represents a small molecule compound that can bind to a defective protein and influence its conformation; where LINK represents an optional linking group that is used to conjugate the Targeting Group to the DRUG; and where R represents a substituent to provide for improved transport of the pharmacological chaperone into a cell, wherein R can be removed by an endogenous enzyme activity within the cell, thus allowing the pharmacological chaperone to interact with a defective protein in the cell; and B. administering a therapeutically effective amount of said targeted pharmacological chaperone to a subject suffering from a disease caused by a defective protein.