Chaperone, pharmacological

A number of different low molecular weight compounds are known to stablize proteins in their native conformation and, therefore, may be effective in correcting of protein folding abnormalities in vivo. Relevant compounds are iV-acetyl-L-lysine, L-camitine, taurine, betaine, ectoine, and hydroxy-ectoine [4]. Some of these chemical chaperones and pharmacological chaperones are already used in clinical trials to combat protein folding diseases, such as cystic fibrosis. 

Protein Trafficking and Quality Control. Table 1 Examples of diseases associated with folding-defective, mutant proteins, and pharmacological chaperones used to correct misfolding in vitro... 

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. 

RL, Wustman BA, Huertas P, Powe AC, Pine CW, Khanna R, Schlossmacher MG Ringe D, Petsko GA. (2007) Stracture of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat Chem Biol 3 101-107. 

Steet R, Chung S, Lee WS, Pine CW, Do H, Komfeld S. (2007) Selective action of the iminosugar isofagomine, a pharmacological chaperone for mutant forms of acid-beta-glucosidase. Biochem Pharmacol 73 1376-1383. 

R. L. Lieberman, B. A. Wustman, P. Huertas, A. C. Powe, Jr., C. W. Pine, R. Khanna, M. G. Schlossmacher, D. Ringe, and G. A. Petsko, Structure of acid p-glucosidase with pharmacological chaperone provides insight into Gaucher disease, Nat. Chem. Biol., 3 (2007) 101-107. 

L. Yu, K. Ikeda, A. Kato, I. Adachi, G. Godin, P. Compain, O. Martin, and N. Asano, a-l-C-Octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease, Bioorg. Med. Chem., 14 (2006) 7736-7744. 

O. R. Martin, Second-generation iminoxylitol-based pharmacological chaperones for the treatment of Gaucher disease, ChemMedChem, 6 (2011) 353-361. 

Petaja-Repo, U. E., Hogue, M., Bhalla, S., Laperriere, A., Morello, J. P., and Bouvier, M. (2002). Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBOJ. 21, 1628-1637. 

Fig. 5.11 Structures of pharmacological chaperones for lysosomal storage disorders.

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