Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Q&A: What are pharmacological chaperones and why are they interesting? | Journal of Biology Question Answer Q A What are pharmacological chaperones and why are they interesting Dagmar Ringe and Gregory A Petsko Address Departments of Biochemistry and Chemistry and the Rosenstiel Center Brandeis University 415 South Street Waltham MA 02454 USA. Correspondence Gregory A Petsko. Email petsko@. Dagmar Ringe. Email ringe@ What is a chaperone in the context of pharmacology The term chaperone is borrowed from the name of a class of proteins that function in living cells 1 . Protein molecules are usually only marginally stable under physiological conditions so some percent of them are often unfolded or misfolded. Such molecules can aggregate with one another or with properly functioning proteins with deleterious consequences to the cell. Protein chaperones prevent these unwanted associations by sequestering unfolded and misfolded proteins and providing them with an environment in which they have the opportunity to refold properly. In addition the interior of a living cell is an extremely crowded environment in which the concentration of macromolecules may exceed 100 pM 2 3 . As a protein is being synthesized on the ribosome protein chaperones protect the nascent polypeptide chain from undesirable associations in that crowded environment until it can fold properly. In pharmacology the role of a chaperone is similar but instead of being proteins pharmacological chaperones are small molecules and instead of assisting in folding they usually stabilize an already folded macromolecule usually a protein by binding to it and stabilizing it against thermal denaturation and proteolytic degradation 4-6 . So a pharmacological chaperone is a chemical chaperone No a chemical chaperone is subtly different. Typical chemical chaperones are molecules such as glycerol and trehalose. Pharmacological chaperones are a special subset of chemical chaperones. Molecules like glycerol and trehalose are nonspecific they bind to and stabilize .
