biostudies-literatureOresic Bender KNIBIB NIH HHSEuropean Research CouncilTechnologiestichting STWNIAID NIH HHSNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Institute of General Medical SciencesNational Institute of Biomedical Imaging and BioengineeringNIGMS NIH HHSKWF Kankerbestrijding4771-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC4747655biostudies-literatureUnknown137(14)The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins. Here we present the design and synthesis of a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells. Importantly, this high degree of selectivity is retained both in vitro and in vivo. In combination with a new green-fluorescent pan-reactive cysteine Journal of the American Chemical SocietyDesign of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.PMC4747655R01 EB005011R01 GM054051AI0554752690193R01EB005011-06S1KUN2009-4402R01 HL116307Li HVerdoes MOresic Bender KSanchez Lopez MChowdhury SFigdor CGDatta GKSegal EBogyo MOfori LMock EDEllman JAvan der Linden WAfalseDesign of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins. Here we present the design and synthesis of a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells. Importantly, this high degree of selectivity is retained both in vitro and in vivo. In combination with a new green-fluorescent pan-reactive cysteine 2015-01-01T00:00:00Z2015 Apr2026-05-05T08:32:06.075Z2026-04-07T21:35:23.226ZS-EPMC47476552578554010.1021/jacs.5b00315