On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences
Citations Over Time
Abstract
A new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. As target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (Plasmodium falciparum) and African sleeping sickness (Trypanosoma brucei rhodesiense). The best inhibitors with unusual amino acid sequences not reported before for this type of enzyme were also fully analyzed in detail in solution. K(i) values in the lower micromolar and even nanomolar region were found. Some inhibitors are even active against plasmodia and show good selectivity relative to other enzymes. Also the mechanism of action was studied and could be shown to be irreversible inhibition.
Related Papers
- → Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain(2015)18 cited
- → A study to Determine the Toxicity of Fumaric Acid*†(1946)25 cited
- Study on content changes of fumaric acid in Sarcandrae(2012)
- Effects of Exogenous Supplement on Fermentative Production of Fumaric Acid by Rhizopupus oryzae(2009)
- A Greener Method for the Preparation of Fumaric Acid and Malic Acid from Maleic Acid(2010)