用于蛋白酶激活受体2（PAR2）的高亲和力荧光探针。
High Affinity Fluorescent Probe for Proteinase-Activated Receptor 2 (PAR2).
作者信息
LeSarge Jordan C, Thibeault Pierre, Milne Mark, Ramachandran Rithwik, Luyt Leonard G
机构信息
Department of Chemistry, Department of Physiology and Pharmacology, Department of Oncology, and Department of Medical Imaging, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7, Canada.
London Regional Cancer Program, Lawson Health Research Institute, 800 Commissioners Road East, London, Ontario N6A 5W9, Canada.
出版信息
ACS Med Chem Lett. 2019 Jun 6;10(7):1045-1050. doi: 10.1021/acsmedchemlett.9b00094. eCollection 2019 Jul 11.
PAR2 is a proteolytically activated G protein-coupled receptor (GPCR) that is implicated in various cancers and inflammatory diseases. Ligands with low nanomolar affinity for PAR2 have been developed, but there is a paucity of research on the development of PAR2-targeting imaging probes. Here, we report the development of seven novel PAR2-targeting compounds. Four of these compounds are highly potent and selective PAR2-targeting peptides (EC = 10 to 23 nM) that have a primary amine handle available for facile conjugation to various imaging components. We describe a peptide of the sequence Isox-Cha-Chg-ARK(Sulfo-Cy5)-NH as the most potent and highest affinity PAR2-selective fluorescent probe reported to date (EC = 16 nM, = 38 nM). This compound has a greater than 10-fold increase in potency and binding affinity for PAR2 compared to the leading previously reported probe and is conjugated to a red-shifted fluorophore, enabling and studies.
蛋白酶激活受体2（PAR2）是一种经蛋白水解激活的G蛋白偶联受体（GPCR），与多种癌症和炎症性疾病有关。已开发出对PAR2具有低纳摩尔亲和力的配体，但针对PAR2的成像探针开发研究较少。在此，我们报告了七种新型PAR2靶向化合物的开发。其中四种化合物是高效且选择性的PAR2靶向肽（EC = 10至23 nM），具有伯胺基团，便于与各种成像组件进行共轭。我们描述了序列为Isox-Cha-Chg-ARK（Sulfo-Cy5）-NH的肽，它是迄今为止报道的最有效且亲和力最高的PAR2选择性荧光探针（EC = 16 nM， = 38 nM）。与先前报道的领先探针相比，该化合物对PAR2的效力和结合亲和力提高了10倍以上，并与红移荧光团共轭，可用于 和 研究。
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