Inflammatory caspases, caspases 1, 4 and 5 in humans, are cysteine-dependent aspartic acid-directed proteases which are activated as part of the NLR3P inflammasome and involved in the innate immune response. Caspases are overactive in many inflammatory diseases such as arthritis, lupus and others. Induced by pathogen associated molecular patterns (PAMPs) or damage associated molecular patterns (DAMPs), caspases initiate an immune response by cleaving their natural substrates gasdermin D and interleukin-1β. The study of caspases, their role in inflammatory disorders and the development of caspase inhibitors are currently limited by the need for substrates which are selective for each caspase. A Förster resonance energy transfer (FRET) based assay was used to obtain observed rate constants for multiple substrates with the inflammatory caspases. Substrates with kobs values of at least 0.01 min–1 were subjected to detailed Michaelis-Menten kinetics analyses. The kinetic parameters obtained were used to create selectivity and specificity profiles for each caspase. The development of selective substrates will allow for differentiation between inflammatory caspases and thus a more thorough understanding of their inflammatory pathway.

Kinetic analysis of peptide FRET substrates for inflammatory caspases

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.