• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

基于氨基磷酸酯的膜型-1基质金属蛋白酶拟肽抑制剂。

Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.

作者信息

Mendes Desiree E, Wong-On-Wing Annie, Berkman Clifford E

机构信息

a Department of Chemistry , Washington State University , Pullman , Washington , DC , USA.

出版信息

J Enzyme Inhib Med Chem. 2016;31(1):167-71. doi: 10.3109/14756366.2015.1010528. Epub 2015 Sep 4.

DOI:10.3109/14756366.2015.1010528
PMID:25815671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4701619/
Abstract

Membrane-type I matrix metalloproteinases (MT1-MMP) is an enzyme critical to the remodeling and homeostasis of extracellular matrix, and when over expressed it contributes to metastasis and cancer cell progression. Because of its role and implication as a biomarker that is upregulated in various cancers, MT1-MMP has become an attractive target for drug discovery. A small pilot library of peptidomimetics containing a phosphoramidate core as a zinc-binding group was synthesized and tested for inhibitory potency against MT1-MMP. From this library, a novel two residue peptidomimetic scaffold was identified that confers potency against MT1-MMP at submicromolar concentrations. The results of this study confirm that for this scaffold, valine is favored as a P1 residue and leucine in the P1' position. Furthermore, steric tolerance was observed for the N-terminus, thus implicating that a second-generation library could be constructed to extend the scaffold to P2 without concomitant loss of affinity within the MT1-MMP catalytic domain.

摘要

膜型I基质金属蛋白酶(MT1-MMP)是一种对细胞外基质重塑和稳态至关重要的酶,当其过度表达时会促进转移和癌细胞进展。由于其作为多种癌症中上调的生物标志物的作用和意义,MT1-MMP已成为药物研发的一个有吸引力的靶点。合成了一个包含磷酰胺核心作为锌结合基团的小型拟肽先导库,并测试了其对MT1-MMP的抑制效力。从该库中鉴定出一种新型的双残基拟肽支架,其在亚微摩尔浓度下对MT1-MMP具有效力。这项研究的结果证实,对于这种支架,缬氨酸作为P1残基是有利的,而亮氨酸位于P1'位置。此外,在N端观察到空间耐受性,因此意味着可以构建第二代文库,将支架扩展到P2,而不会在MT1-MMP催化结构域内同时丧失亲和力。

相似文献

1
Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.基于氨基磷酸酯的膜型-1基质金属蛋白酶拟肽抑制剂。
J Enzyme Inhib Med Chem. 2016;31(1):167-71. doi: 10.3109/14756366.2015.1010528. Epub 2015 Sep 4.
2
Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis.选择性功能阻断单克隆人抗体突出了膜型-1基质金属蛋白酶(MT1-MMP)在转移中的重要作用。
Oncotarget. 2017 Jan 10;8(2):2781-2799. doi: 10.18632/oncotarget.13157.
3
Design, synthesis and biological evaluation of ferulic Acid amides as selective matrix metalloproteinase inhibitors.阿魏酸酰胺类化合物的设计、合成与生物评价及其作为选择性基质金属蛋白酶抑制剂的研究
Med Chem. 2013 Nov;9(7):947-54. doi: 10.2174/1573406411309070008.
4
Synthesis and structure-activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors.咖啡酸酰胺类化合物的合成及结构-活性关系研究作为选择性基质金属蛋白酶抑制剂。
Bioorg Med Chem Lett. 2013 Mar 1;23(5):1206-11. doi: 10.1016/j.bmcl.2013.01.027. Epub 2013 Jan 16.
5
The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen.前列腺特异性膜抗原的氨基磷酸肽模拟抑制剂的分子剪裁
Bioorg Med Chem. 2007 Dec 1;15(23):7434-43. doi: 10.1016/j.bmc.2007.07.028. Epub 2007 Aug 21.
6
Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation via Ugi bis-amide synthesis.针对 MMP-9 的战斗策略;通过 Ugi 双酰胺合成发现具有 PI3K/AKT 信号抑制和 caspase 3/7 激活作用的新型非羟肟酸 MMP-9 抑制剂。
Eur J Med Chem. 2020 Jan 15;186:111875. doi: 10.1016/j.ejmech.2019.111875. Epub 2019 Nov 10.
7
Inhibition of enzyme activity of and cell-mediated substrate cleavage by membrane type 1 matrix metalloproteinase by newly developed mercaptosulphide inhibitors.新型巯基硫化物抑制剂对膜型1基质金属蛋白酶的酶活性及细胞介导的底物裂解的抑制作用。
Biochem J. 2005 Dec 15;392(Pt 3):527-36. doi: 10.1042/BJ20050545.
8
Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer.用于前列腺癌PET成像的(18)F标记的磷酰胺肽模拟前列腺特异性膜抗原(PSMA)靶向抑制剂类似物的构效关系
J Med Chem. 2016 Jun 23;59(12):5684-94. doi: 10.1021/acs.jmedchem.5b01850. Epub 2016 Jun 13.
9
Design, synthesis and biological evaluation of bifunctional inhibitors of membrane type 1 matrix metalloproteinase (MT1-MMP).设计、合成及膜型 1 基质金属蛋白酶(MT1-MMP)双功能抑制剂的生物学评价。
Bioorg Med Chem. 2019 Jan 1;27(1):196-207. doi: 10.1016/j.bmc.2018.11.041. Epub 2018 Nov 29.
10
Design, synthesis and preliminary evaluation of α-sulfonyl γ-(glycinyl-amino)proline peptidomimetics as matrix metalloproteinase inhibitors.α-磺酰基γ-(甘氨酰氨基)脯氨酸拟肽作为基质金属蛋白酶抑制剂的设计、合成及初步评价
Bioorg Med Chem. 2014 Jun 1;22(11):3055-64. doi: 10.1016/j.bmc.2013.12.025. Epub 2013 Dec 21.

引用本文的文献

1
The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma.基质金属蛋白酶抑制剂的复兴:超越教条。
Cells. 2019 Aug 27;8(9):984. doi: 10.3390/cells8090984.

本文引用的文献

1
Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.内体WASH和外排体复合物控制侵袭伪足处MT1-MMP的胞吐作用。
J Cell Biol. 2013 Dec 23;203(6):1063-79. doi: 10.1083/jcb.201306162.
2
Selective blockade of matrix metalloprotease-14 with a monoclonal antibody abrogates invasion, angiogenesis, and tumor growth in ovarian cancer.用单克隆抗体选择性阻断基质金属蛋白酶-14 可破坏卵巢癌的侵袭、血管生成和肿瘤生长。
Cancer Res. 2013 Apr 15;73(8):2457-2467. doi: 10.1158/0008-5472.CAN-12-1426. Epub 2013 Feb 19.
3
Novel MT1-MMP small-molecule inhibitors based on insights into hemopexin domain function in tumor growth.基于对血红素结合蛋白结构域在肿瘤生长中功能的深入了解,设计新型 MT1-MMP 小分子抑制剂。
Cancer Res. 2012 May 1;72(9):2339-49. doi: 10.1158/0008-5472.CAN-11-4149. Epub 2012 Mar 9.
4
Inhibition of matrix metalloproteinase 14 (MMP-14)-mediated cancer cell migration.抑制基质金属蛋白酶 14(MMP-14)介导的癌细胞迁移。
J Biol Chem. 2011 Sep 23;286(38):33167-77. doi: 10.1074/jbc.M111.256644. Epub 2011 Jul 27.
5
High-affinity peptide against MT1-MMP for in vivo tumor imaging.针对 MT1-MMP 的高亲和力肽用于体内肿瘤成像。
J Control Release. 2011 Mar 30;150(3):248-55. doi: 10.1016/j.jconrel.2011.01.032. Epub 2011 Feb 2.
6
The intrinsic protein flexibility of endogenous protease inhibitor TIMP-1 controls its binding interface and affects its function.内源性蛋白酶抑制剂 TIMP-1 的固有蛋白灵活性控制其结合界面并影响其功能。
Biochemistry. 2010 Jul 27;49(29):6184-92. doi: 10.1021/bi902141x.
7
A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth.一种新型、选择性的膜型基质金属蛋白酶-1(MT1-MMP)抑制剂可降低癌细胞的迁移能力和肿瘤生长。
Cancer Biol Ther. 2009 Dec;8(24):2362-70. doi: 10.4161/cbt.8.24.10139. Epub 2009 Dec 19.
8
Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis.基质金属蛋白酶-14的选择性抑制可阻断肿瘤生长、侵袭和血管生成。
Cancer Res. 2009 Feb 15;69(4):1517-26. doi: 10.1158/0008-5472.CAN-08-3255. Epub 2009 Feb 10.
9
Proteolytic interstitial cell migration: a five-step process.蛋白水解性间质细胞迁移:一个五步过程。
Cancer Metastasis Rev. 2009 Jun;28(1-2):129-35. doi: 10.1007/s10555-008-9174-3.
10
Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion.多步骤细胞周缘蛋白水解作用控制着癌细胞从个体侵袭向集体侵袭的转变。
Nat Cell Biol. 2007 Aug;9(8):893-904. doi: 10.1038/ncb1616. Epub 2007 Jul 8.