A disintegrin and metalloproteinase (ADAMs) are membrane‐bound metalloproteases responsible for the ectodomain shedding of various transmembrane proteins and play important roles in multiple relevant biological processes. Their altered expression is involved in several pathological conditions, and in particular ADAM10 or ADAM17 overexpression is found in various forms of cancer. To better understand how they are regulated in the cellular context, it is useful to visualize the specific ADAMs pathway by means of molecular imaging techniques. For this purpose, we synthesized bioactive fluorescent probes suitable for cell imaging and that are able to specifically target ADAM10 or ADAM17. Two previously developed ADAM17‐ and ADAM10‐selective inhibitors were chosen for conjugation, respectively, to a Cy5.5 dye and to Cy5.5 and FITC dyes. Herein we also report the synthesis of a gold‐labeled compound as an additional bioimaging probe for ADAM10. The newly synthesized ligands were found to be active in vitro on human recombinant ADAM10 and/or ADAM17, showing IC₅₀ values in the nanomolar range and a good selectivity over matrix metalloproteinases (MMPs). Finally, these newly developed probes were successfully used for ADAMs staining on different lymphoma cell lines and lymph node mesenchymal stromal cells.

中文翻译：

---

ADAM10和ADAM17高选择性生物成像探针的合成与体外评价

甲d isintegrin一个第二米etalloproteinase（ADAMs）是膜结合的金属蛋白酶，负责各种跨膜蛋白的胞外域脱落，并在多个相关的生物学过程中发挥重要作用。它们的表达改变与几种病理状况有关，尤其是在各种形式的癌症中都发现了ADAM10或ADAM17过表达。为了更好地了解它们在细胞环境中的调控方式，通过分子成像技术可视化特定的ADAM途径非常有用。为此，我们合成了适用于细胞成像并且能够特异性靶向ADAM10或ADAM17的生物活性荧光探针。选择了两种先前开发的ADAM17和ADAM10选择性抑制剂分别与Cy5.5染料，Cy5.5和FITC染料结合。在这里，我们还报告了金标记化合物的合成，作为ADAM10的另一种生物成像探针。发现新合成的配体在体外对人重组ADAM10和/或ADAM17有活性，显示出IC在纳摩尔范围内具有_50个值，并且相对于基质金属蛋白酶（MMP）具有良好的选择性。最后，这些新开发的探针已成功用于不同淋巴瘤细胞系和淋巴结间充质基质细胞的ADAM染色。