Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts.
Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts.
复制标题
DOI：
10.1002/anie.202006719
复制
发表时间：
2020-10-19
期刊：
影响因子：
--
通讯作者：
Bogyo M
中科院分区：
文献类型：
--
作者：
Tholen M;Yim JJ;Groborz K;Yoo E;Martin BA;van den Berg NS;Drag M;Bogyo M
Fluorescently-quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection and surgical guidance. These probes are often designed to target specific enzymes associated with disease by direct optimization using single purified enzymes. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when applied in vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino acid residues that was used to generate highly efficient tumor-specific probes. This new strategy simplifies and enhances the process of probe optimization without any a priori knowledge of enzyme targets and has the potential to be applied to diverse disease states using clinical or animal model tissues samples. Proteolytic profiling of disease tissue lysates using highly diverse substrate libraries enables streamlined development of in vivo imaging probes and diagnostics without prior knowledge of target enzymes.
登录
查看更多内容
荧光引导的手术和实时导航 - 一种新的尖端。
DOI：
10.1038/nrc3566
发表时间：
2013-09
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.4
作者：
Choi KY;Swierczewska M;Lee S;Chen X
通讯作者：
Chen X
影响因子：
8.4
作者：
Poreba, Marcin;Groborz, Katarzyna;Salvesen, Guy S.
通讯作者：
Salvesen, Guy S.
影响因子：
8.4
作者：
Poreba M;Rut W;Vizovisek M;Groborz K;Kasperkiewicz P;Finlay D;Vuori K;Turk D;Turk B;Salvesen GS;Drag M
通讯作者：
Drag M
影响因子：
--
作者：
Edgington, Laura E.;van Raam, Bram J.;Bogyo, Matthew
通讯作者：
Bogyo, Matthew