Inhibition of Neutrophil Elastase and Cathepsin G As a New Approach to the Treatment of Psoriasis: From Fundamental Biology to Development of New Target-Specific Drugs

Krasavin M. Yu; Gureev M. A.; Garabadzhiu A. V; Pashkin A. Yu; Zhukov A. S.; Khairutdinov V. R.; Samtsov A. V; Shvets V. I

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Inhibition of Neutrophil Elastase and Cathepsin G As a New Approach to the Treatment of Psoriasis: From Fundamental Biology to Development of New Target-Specific Drugs

机译：嗜中性粒细胞弹性蛋白酶和组织蛋白酶G的抑制作为治疗牛皮癣的一种新方法：从基础生物学到开发新的针对特定目标的药物

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Psoriasis therapy remains an extremely relevant area of modern drug design, due to necessity of adverse reaction reduction, inherent for actual methods of therapy. It was established that two serine proteases-neutrophil elastase 1 (HNE1) and cathepsin G (CatG)-are the key agents in psoriasis development. The collected molecular data for the presented targets form the basis for the molecular modeling strategy for the search for and identification of new target-specific inhibitors. The result of this work is a group of high-priority small-molecule compounds with double-targeted affinity, which are able to suppress the pro-psoriatic processes induced by the considered serine proteases at the initial stage of the disease.

机译：由于必须减少实际治疗方法固有的不良反应，因此牛皮癣治疗仍然是现代药物设计中极为重要的领域。已经确定，两种丝氨酸蛋白酶中性粒细胞弹性蛋白酶1（HNE1）和组织蛋白酶G（CatG）是牛皮癣发展的关键药物。所收集靶标的分子数据构成了分子建模策略的基础，该策略用于寻找和鉴定新的靶标特异性抑制剂。这项工作的结果是一组具有双重目标亲和力的高优先级小分子化合物，它们能够在疾病初期抑制由考虑的丝氨酸蛋白酶诱导的促银屑病过程。

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《Doklady biochemistry & biophysics》 |2019年第julaaug期|272-276|共5页
作者
Krasavin M. Yu; Gureev M. A.; Garabadzhiu A. V; Pashkin A. Yu; Zhukov A. S.; Khairutdinov V. R.; Samtsov A. V; Shvets V. I;
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St Petersburg State Univ St Petersburg 199034 Russia;

St Petersburg State Technol Inst Tech Univ St Petersburg 190013 Russia|Sechenov First Moscow State Med Univ Moscow 119991 Russia;

St Petersburg State Technol Inst Tech Univ St Petersburg 190013 Russia;

Kirov Mil Med Acad St Petersburg 194044 Russia;

St Petersburg State Technol Inst Tech Univ St Petersburg 190013 Russia|Russian Technol Univ Lomonosov Inst Fine Chem Technol MIREA Moscow 119454 Russia|Res Inst Gen Pathol & Pathophysiol Moscow 125315 Russia;

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1. Lysosomal elastase and cathepsin G in beige mice. Neutrophils of beige (Chediak-Higashi) mice selectively lack lysosomal elastase and cathepsin G. [J] . K Takeuchi, H Wood, R T Swank The Journal of Experomental Medicine . 1986,第3期

机译：米色小鼠的溶酶体弹性蛋白酶和组织蛋白酶G。米色（Chediak-Higashi）小鼠的中性粒细胞选择性缺乏溶酶体弹性蛋白酶和组织蛋白酶G。
2. Phosphoinositide 3‐kinase inhibition reverses platelet aggregation triggered by the combination of the neutrophil proteinases elastase and cathepsin G without impairing αIIbβ3 integrin activation [J] . Balloy Viviane, Chap Hugues, Chignard Michel, FEBS Letters . 2000,第3期

机译：磷酸肌醇3激酶抑制作用可逆转中性粒细胞蛋白酶弹性蛋白酶和组织蛋白酶G触发的血小板聚集，而不会损害αIIbβ3整联蛋白的活化
3. Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses [J] . Hikari Koga, Nobuaki Miyahara, Yasuko Fuchimoto, Respiratory Research . 2013,第1期

机译：在继发性变应原攻击的小鼠模型中，嗜中性粒细胞弹性蛋白酶的抑制作用减弱气道高反应性和炎症：嗜中性粒细胞弹性蛋白酶的抑制作用减弱呼吸道过敏性反应
4. Tyrosine-derived and drug-loaded nanospheres for the topical treatment of psoriasis [C] . Zheng Zhang, Larisa Sheihet, Brian Kilfoyle, World biomaterials congress . 2012

机译：酪氨酸衍生和载药纳米球用于牛皮癣的局部治疗
5. In silico screening for novel inhibitors of human neutrophil elastase using an integrated approach of quantitative structure activity relationship modeling and protein-ligand docking. [D] . Nguyen, Christian V. 2014

机译：在计算机上使用定量结构活性关系建模和蛋白质-配体对接的集成方法筛选人类嗜中性粒细胞弹性蛋白酶的新型抑制剂。
6. Lysosomal elastase and cathepsin G in beige mice. Neutrophils of beige (Chediak-Higashi) mice selectively lack lysosomal elastase and cathepsin G [O] . 1986

机译：米色小鼠的溶酶体弹性蛋白酶和组织蛋白酶G。米色（Chediak-Higashi）小鼠的嗜中性粒细胞选择性缺乏溶酶体弹性蛋白酶和组织蛋白酶G
7. Inhibition of neutrophil elastase and cathepsin G as a new approach to the treatment of psoriasis: from fundamental biology to development of new target-specific drugs [O] . M. Y. Krasavin, M. A. Gureev, А. V. Garabadzhiu, 2019

机译：抑制嗜中性粒细胞弹性蛋白酶和组织蛋白酶G作为治疗牛皮癣的新方法：从基本生物学到新的靶特异性药物的发展
8. Structural Biology and Protein Engineering Approach to the Development of Antidotes Against the Inhibition of Human Acetylcholinesterase by OP-based Nerve Agents. [R] . Sussman, J. L., Tawfik, D. S. 2015

机译：结构生物学和蛋白质工程方法开发抗Op基神经毒剂抑制人乙酰胆碱酯酶的解毒剂。

Inhibition of Neutrophil Elastase and Cathepsin G As a New Approach to the Treatment of Psoriasis: From Fundamental Biology to Development of New Target-Specific Drugs

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