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Prodrug-inspired probes selective to cathepsin B over other cysteine cathepsins.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chowdhury MA,Moya IA,Bhilocha S,McMillan CC,Vigliarolo BG,Zehbe I,Phenix CP

doi

10.1021/jm500544p

subject

Has Abstract

pub_date

2014-07-24 00:00:00

pages

6092-104

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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