Chemical/pharmacological chaperone strategies

Chemical/pharmacological chaperone strategies aim at correcting this impaired folding through stabilization of the enzyme in its proper fold, which can be achieved by inhibition of the enzyme active site. The caveat of this strategy... 

Neither chemical nor pharmacological chaperones lead to wild-type expression levels of the mutant proteins at the cell surface. Alternative or additional strategies are needed to improve the intracellular transport of the mutant proteins. In the future, dtugs may also be developed that influence those components of the quality control system that are involed in the retention of misfolded proteins. 

Burrows JA, Willis LK, Perlmutter DH. Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z A potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency. Proc. Natl. Acad. Sci. U.S.A. 2000 97 1796-1801. 

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