25 research outputs found
Prodrug-Inspired Probes Selective to Cathepsin B over Other Cysteine Cathepsins
Cathepsin
B (CTB) is a cysteine protease believed to be an important
therapeutic target or biomarker for several diseases including aggressive
cancer, arthritis, and parasitic infections. The development of probes
capable of assessing CTB activity in cell lysates, living cells, and
animal models of disease are needed to understand its role in disease
progression. However, discovering probes selective to cathepsin B
over other cysteine cathepsins is a significant challenge due to overlap
of preferred substrates and binding site homology in this family of
proteases. Herein we report the synthesis and detailed evaluation
of two prodrug-inspired fluorogenic peptides designed to be efficient
and selective substrate-based probes for CTB. Through cell lysate
and cell assays, a promising lead candidate was identified that is
efficiently processed and has high specificity for CTB over other
cysteine cathepsins. This work represents a key step toward the design
of rapid release prodrugs or substrate-based molecular imaging probes
specific to CTB