赖氨酰氟甲烷的合成及其作为胰蛋白酶、纤溶酶和组织蛋白酶B抑制剂的性质。
The synthesis of lysylfluoromethanes and their properties as inhibitors of trypsin, plasmin and cathepsin B.
作者信息
Angliker H, Wikstrom P, Rauber P, Shaw E
出版信息
Biochem J. 1987 Feb 1;241(3):871-5. doi: 10.1042/bj2410871.
Abstract
The synthesis of two lysylfluoromethanes is described by an extension of the synthesis method of Rauber, Angliker, Walker & Shaw [(1986) Biochem. J. 239, 633-640]. Ala-Phe-Lys-CH2F was found to be an active-centre-directed inhibitor of plasmin and trypsin, as is the corresponding chloromethane. However, the rate of covalent-bond formation is about an order of magnitude lower at 25 degrees C for the fluoro derivative. It was, in addition, an extremely effective inactivator of cathepsin B at pH 5.4 and 6.4. The chemical reactivity of fluoromethanes was compared with that of chloromethanes as alkylators of GSH. At pH 7.4 and 37 degrees C, a fluoromethane has 1/500th the reactivity of a chloromethane. A comparison of the rates of reaction of the fluoromethane with cathepsin B and with GSH at pH 6.4 revealed an enhancement of 10(8)-fold for the alkylation of the enzyme, ascribable largely to a proximity effect.
摘要
通过扩展劳伯、安利克、沃克和肖的合成方法[（1986年）《生物化学杂志》239卷，633 - 640页]描述了两种赖氨酰氟甲烷的合成。发现丙氨酰 - 苯丙氨酰 - 赖氨酰 - 甲基氟（Ala - Phe - Lys - CH₂F）是纤溶酶和胰蛋白酶的活性中心导向抑制剂，相应的氯甲烷也是如此。然而，在25℃时，氟代衍生物的共价键形成速率比氯代衍生物低约一个数量级。此外，它在pH 5.4和6.4时是组织蛋白酶B的极其有效的失活剂。将氟甲烷与氯甲烷作为谷胱甘肽（GSH）烷基化剂的化学反应性进行了比较。在pH 7.4和37℃时，氟甲烷的反应活性是氯甲烷的1/500。在pH 6.4时，氟甲烷与组织蛋白酶B和与谷胱甘肽的反应速率比较显示，酶烷基化的增强了10⁸倍，这主要归因于邻近效应。
相似文献
1
The synthesis of lysylfluoromethanes and their properties as inhibitors of trypsin, plasmin and cathepsin B.赖氨酰氟甲烷的合成及其作为胰蛋白酶、纤溶酶和组织蛋白酶B抑制剂的性质。
Biochem J. 1987 Feb 1;241(3):871-5. doi: 10.1042/bj2410871.
2
The synthesis of peptidylfluoromethanes and their properties as inhibitors of serine proteinases and cysteine proteinases.肽基氟甲烷的合成及其作为丝氨酸蛋白酶和半胱氨酸蛋白酶抑制剂的性质。
Biochem J. 1986 Nov 1;239(3):633-40. doi: 10.1042/bj2390633.
3
Synthesis and properties of peptidyl derivatives of arginylfluoromethanes.精氨酰氟甲烷的肽基衍生物的合成与性质
Biochem J. 1988 Dec 1;256(2):481-6. doi: 10.1042/bj2560481.
4
Visualization of time-dependent inactivation of human tumor cathepsin B isozymes by a peptidyl fluoromethyl ketone using a fluorescent print technique.
Anticancer Res. 1988 Jul-Aug;8(4):525-9.
5
Peptidyl fluoromethyl ketones as thiol protease inhibitors.作为硫醇蛋白酶抑制剂的肽基氟甲基酮。
Biomed Biochim Acta. 1986;45(11-12):1397-403.
6
The synthesis, kinetic characterization and application of a novel biotinylated affinity label for cathepsin B.一种新型组织蛋白酶B生物素化亲和标记物的合成、动力学表征及应用
Biochem J. 1992 Apr 15;283 ( Pt 2)(Pt 2):449-53. doi: 10.1042/bj2830449.
7
Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis.肽基氟甲基酮作为组织蛋白酶B的抑制剂。对类风湿性关节炎治疗的意义。
Biochem Pharmacol. 1992 Sep 25;44(6):1201-7. doi: 10.1016/0006-2952(92)90385-v.
8
Peptides containing acylated C-terminal gem diamines: novel irreversible inactivators of the cysteine and serine proteinases.
Chem Biol Drug Des. 2006 May;67(5):364-9. doi: 10.1111/j.1747-0285.2006.00390.x.
9
Synthesis and properties of Cbz-Phe-Arg-CHN2 (benzyloxycarbonylphenylalanylarginyldiazomethane) as a proteinase inhibitor.作为蛋白酶抑制剂的苄氧羰基苯丙氨酰精氨酰重氮甲烷（Cbz-Phe-Arg-CHN2）的合成与性质
Biochem J. 1988 Mar 1;250(2):621-3. doi: 10.1042/bj2500621.
引用本文的文献
1
Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry.肽基氟甲基酮及其在药物化学中的应用。
Molecules. 2020 Sep 3;25(17):4031. doi: 10.3390/molecules25174031.
2
Design, Synthesis and Biological Evaluation of Jahanyne Analogs as Cell Cycle Arrest Inducers.设计、合成及 Jahanyne 类似物的细胞周期阻滞诱导活性的生物评价。
Mar Drugs. 2020 Mar 23;18(3):176. doi: 10.3390/md18030176.
3
Development of a covalent inhibitor of gut bacterial bile salt hydrolases.肠道细菌胆盐水解酶共价抑制剂的开发。
Nat Chem Biol. 2020 Mar;16(3):318-326. doi: 10.1038/s41589-020-0467-3. Epub 2020 Feb 10.
4
The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress.组织蛋白酶 B 抑制剂 z-FA-CMK 通过氧化应激诱导白血病 T 细胞死亡。
Naunyn Schmiedebergs Arch Pharmacol. 2018 Jan;391(1):71-82. doi: 10.1007/s00210-017-1436-6. Epub 2017 Oct 31.
5
Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors.半胱氨酸蛋白酶作为治疗靶点：选择性重要吗？对钙蛋白酶和组织蛋白酶抑制剂的系统评价。
Acta Pharm Sin B. 2015 Nov;5(6):506-19. doi: 10.1016/j.apsb.2015.08.001. Epub 2015 Sep 26.
6
Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress.组织蛋白酶B抑制剂z-FA-FMK介导的人T细胞增殖抑制是由氧化应激引起的。
PLoS One. 2015 Apr 27;10(4):e0123711. doi: 10.1371/journal.pone.0123711. eCollection 2015.
7
Chemical genetic strategy for targeting protein kinases based on covalent complementarity.基于共价互补性的靶向蛋白激酶的化学遗传策略。
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15046-52. doi: 10.1073/pnas.1111239108. Epub 2011 Aug 18.
8
Synthesis and properties of peptidyl derivatives of arginylfluoromethanes.精氨酰氟甲烷的肽基衍生物的合成与性质
Biochem J. 1988 Dec 1;256(2):481-6. doi: 10.1042/bj2560481.
9
Pseudoarginine: synthesis and properties of derivatives of delta-(1-imidazolyl)norvaline.伪精氨酸：δ-(1-咪唑基)正缬氨酸衍生物的合成与性质
Biochem J. 1990 Mar 15;266(3):829-34.
10
The synthesis of arginylfluoroalkanes, their inhibition of trypsin and blood-coagulation serine proteinases and their anticoagulant activity.精氨酰氟代烷烃的合成、它们对胰蛋白酶和血液凝固丝氨酸蛋白酶的抑制作用以及它们的抗凝血活性。
Biochem J. 1990 Jan 15;265(2):539-45. doi: 10.1042/bj2650539.
本文引用的文献
1
THE IDENTIFICATION OF THE HISTIDINE RESIDUE AT THE ACTIVE CENTER OF CHYMOTRYPSIN.胰凝乳蛋白酶活性中心组氨酸残基的鉴定
J Biol Chem. 1965 Feb;240:694-8.
2
Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase.甲磺酸酯作为乙酰胆碱酯酶的不可逆抑制剂
J Biol Chem. 1962 Oct;237:3245-9.
3
Direct evidence for the presence of histidine in the active center of chymotrypsin.关于组氨酸存在于胰凝乳蛋白酶活性中心的直接证据。
Biochemistry. 1963 Mar-Apr;2:252-5. doi: 10.1021/bi00902a008.
4
A new method for labelling the active center of chymotrypsin.一种标记胰凝乳蛋白酶活性中心的新方法。
Biochem Biophys Res Commun. 1962 Feb 20;7:36-40. doi: 10.1016/0006-291x(62)90140-7.
5
Tissue sulfhydryl groups.组织巯基
Arch Biochem Biophys. 1959 May;82(1):70-7. doi: 10.1016/0003-9861(59)90090-6.
6
The specificity of cathepsin B.组织蛋白酶B的特异性。
Acta Biol Med Ger. 1981;40(10-11):1503-11.
7
Cathepsin B, Cathepsin H, and cathepsin L.组织蛋白酶B、组织蛋白酶H和组织蛋白酶L。
Methods Enzymol. 1981;80 Pt C:535-61. doi: 10.1016/s0076-6879(81)80043-2.
8
Characterization of a thiol proteinase secreted by malignant human breast tumours.人恶性乳腺肿瘤分泌的一种巯基蛋白酶的特性
Biochim Biophys Acta. 1980 Jul 10;614(1):134-43. doi: 10.1016/0005-2744(80)90174-6.
9
Inactivation of cathepsin B by active site-directed disulfide exchange. Application in covalent affinity chromatography.
J Biol Chem. 1983 Sep 10;258(17):10227-32.
10
Identification of the histidine residue at the active center of trypsin labelled by TLCK.鉴定经甲苯磺酰-L-赖氨酸氯甲基酮（TLCK）标记的胰蛋白酶活性中心的组氨酸残基。
Biochem Biophys Res Commun. 1967 May 5;27(3):391-7. doi: 10.1016/s0006-291x(67)80112-8.
Zotero 插件