Small-molecule catalysts of oxidative protein folding.
Oxidative protein folding occurs both in vivo and in vitro and involves the formation and rearrangement of protein disulfide bonds (SS bonds). In vivo these reactions are catalyzed by enzymes, including the eukaryotic enzyme protein disulfide isomerase (PDI). Using the physical properties of PDI as a guide, several small-molecule catalysts of oxidative protein folding have been designed, synthesized, and tested. These small molecules can improve the folding rate of the model substrate ribonuclease A by a factor of over 10 and improve the yield by up to a factor of 3 over traditional conditions. The molecules have also been demonstrated to significantly improve the in vivo folding of proteins as well.
Lees
Watson J
WJ
Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. leeswj@fiu.edu
D002384:Catalysis / Q000187:drug effects; D004220:Disulfides / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D010084:Oxidation-Reduction; D017510:Protein Folding / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology*
D004220:Disulfides; D054852:Small Molecule Libraries