comparative assessment of substrates and activity based probes as tools for non-invasive optical imaging of cysteine protease activity基板的比较评估和基于活动的调查作为非侵入性的光学成像工具的半胱氨酸蛋白酶活动.pdfVIP

Comparative Assessment of Substrates and Activity Based Probes as Tools for Non-Invasive Optical Imaging of Cysteine Protease Activity 1¤ 2 1 1 1,3 Galia Blum , Robby M. Weimer , Laura E. Edgington , Walter Adams , Matthew Bogyo * 1 Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America, 2 Department of Biomedical Imaging, Genentech Inc., South San Francisco, California, United States of America, 3 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America Abstract Recent advances in the field of non-invasive optical imaging have included the development of contrast agents that report on the activity of enzymatic targets associated with disease pathology. In particular, proteases have proven to be ideal targets for development of optical sensors for cancer. Recently developed contrast agents for protease activity include both small peptides and large polymer-based quenched fluorescent substrates as well as fluorescently labeled activity based probes (ABPs). While substrates produce a fluorescent signal as a result of processing by a protease, ABPs are retained at the site of proteolysis due to formation of a permanent covalent bond with the active site catalytic residue. Both methods have potential advantages and disadvantages yet a careful comparison of substrates and ABPs has not been performed. Here we present the results of a direct comparison of commercially available protease substrates with several recently described fluorescent ABPs in a mouse model of cancer. The results demonstrate that fluorescent ABPs show more rapid and selective