Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds.

ABSTRACT: Peptidyl-proline isomerases (PPIases) are a chaperone superfamily comprising the FK506-binding proteins (FKBPs), cyclophilins, and parvulins. PPIases catalyze the cis/trans isomerization of proline, acting as a regulatory switch during folding, activation, and/or degradation of many proteins. These "clients" include proteins with key roles in cancer, neurodegeneration, and psychiatric disorders, suggesting that PPIase inhibitors could be important therapeutics. However, the active site of PPIases is shallow, solvent-exposed, and well conserved between family members, making selective inhibitor design challenging. Despite these hurdles, macrocyclic natural products, including FK506, rapamycin, and cyclosporin, bind PPIases with nanomolar or better affinity. De novo attempts to derive new cl

SUBMITTER: Dunyak BM 

PROVIDER: S-EPMC5501181 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature