Second-Generation Pharmacological Chaperones: Beyond Inhibitors.

ABSTRACT: Protein misfolding induced by missense mutations is the source of hundreds of conformational diseases. The cell quality control may eliminate nascent misfolded proteins, such as enzymes, and a pathological loss-of-function may result from their early degradation. Since the proof of concept in the 2000s, the bioinspired pharmacological chaperone therapy became a relevant low-molecular-weight compound strategy against conformational diseases. The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Counterintuitively, in binding to the active site, these inhibitors stabilize the proper folding of the mutated protein and partially rescue its cellular function. The main limitation of the first-generation pharmacological chaperones lies in the balance betwe

SUBMITTER: Tran ML 

PROVIDER: S-EPMC7397201 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature