Abstract

In some instances, small molecules can restore function to proteins that are impaired by genetic mutations. There are now many examples where non-specific molecules or specific ligands can act as chemical chaperones to fold proteins or stabilize folded proteins harboring genetic mutations. In contrast a few recent examples have shown that functionally impaired proteins that are stably folded can be “functionally rescued” by appropriate small molecules. Compounds that can rescue functionally impaired proteins may provide new strategies for the treatment of genetic diseases such as rickets and resistance to thyroid hormone (RTH). In addition mutant-complementing analogs and substrates that act exclusively on mutant proteins are providing important tools for the study of complex biological systems that are controlled by molecules that have multiple cellular targets.