Human leukocyte elastase plays a crucial role in a variety of inflammatory disorders and represents an important subject of biomedical studies. The chemotype of peptidic phosphonates was employed for the design of a new activity-based probe for human leukocyte elastase. Its structure combines the phosphonate warhead with an adequate peptide portion and a BODIPY fluorophore with a clickable ethinylphenyl moiety at meso position. The probe 6 was assembled by copper-catalyzed alkyne–azide 1,3-dipolar cycloaddition. It was characterized as an active site-directed elastase inhibitor exhibiting a second-order rate constant of inactivation of 88400 M^–1s^–1. The suitability of 6 as a fluorescent probe for human leukocyte elastase was demonstrated by in-gel fluorescence analysis. Labeling experiments and inhibition data toward a panel of related proteases underlined the selectivity of the probe for the targeted leukocyte elastase.

中文翻译：

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BODIPY标记的膦肽作为人类白细胞弹性蛋白酶的基于活性的探针。

人白细胞弹性蛋白酶在多种炎性疾病中起关键作用，并且是生物医学研究的重要课题。肽膦酸酯的化学型用于设计新的基于活性的人白细胞弹性蛋白酶探针。其结构结合了膦酸酯弹头具有足够的肽部分和BODIPY荧光团与一个可点击的ethinylphenyl部分内消旋位置。探针6由铜催化的炔-叠氮化物1,3-偶极环加成组装而成。它被表征为一种活性的定点弹性蛋白酶抑制剂，具有88400 M ^–1 s ^–1的二级失活速率常数。适合度6通过凝胶内荧光分析证实了其作为人白细胞弹性蛋白酶的荧光探针。针对一组相关蛋白酶的标记实验和抑制数据强调了探针对靶向白细胞弹性蛋白酶的选择性。