高级检索

  • ISSN 1006-3080
  • CN 31-1691/TQ

马来酰亚胺基烯二炔化合物对生物大分子的损伤作用

孙可 鲁浩天 张梦思 胡爱国

孙可, 鲁浩天, 张梦思, 胡爱国. 马来酰亚胺基烯二炔化合物对生物大分子的损伤作用[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20220530002
引用本文: 孙可, 鲁浩天, 张梦思, 胡爱国. 马来酰亚胺基烯二炔化合物对生物大分子的损伤作用[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20220530002
SUN Ke, LU Haotian, ZHANG Mengsi, HU Aiguo. Cleavage of Biological Macromolecules by Maleimide-Based Enediyne Compounds[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20220530002
Citation: SUN Ke, LU Haotian, ZHANG Mengsi, HU Aiguo. Cleavage of Biological Macromolecules by Maleimide-Based Enediyne Compounds[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20220530002

马来酰亚胺基烯二炔化合物对生物大分子的损伤作用

doi: 10.14135/j.cnki.1006-3080.20220530002
基金项目: 国家自然科学基金项目(21871080)
详细信息
    作者简介:

    孙可 (1997-),男,硕士生,主要从事有机小分子合成研究。E-mail:kesunqust@163.com

    通讯作者:

    胡爱国,E-mail:hagmhsn@ecust.edu.cn

  • 中图分类号: O621.3

Cleavage of Biological Macromolecules by Maleimide-Based Enediyne Compounds

  • 摘要: 利用Sonogashira偶联反应合成了3种具有不同羟基数量的马来酰亚胺基烯二炔,它们可以通过马来酰亚胺促进的重排和环芳香化反应(MARACA)作用机制产生高活性的双自由基中间体。电子顺磁共振实验证实了体系中自由基中间体的产生。DNA凝胶电泳实验证实了这些烯二炔能够在生理温度下对质粒DNA产生裂解作用,并表现出浓度依赖性。蛋白质凝胶电泳实验表明它们对蛋白质的降解能力与烯二炔产生自由基的能力一致。对于炔丙位上具有杂原子的高反应活性烯二炔结构,可在低浓度(5 mmol/L)下破坏蛋白质主链结构完整性致使蛋白质失活。研究结果将为探究马来酰亚胺基烯二炔分子对病毒蛋白质等生物大分子的损伤奠定基础,为开发此类分子潜在的临床应用价值提供新的思路。

     

  • 图  1  烯二炔化合物的合成路线

    Figure  1.  Synthetic route of the enediyne compounds

    图  2  EDY-B和EDY-C的核磁共振氢谱

    Figure  2.  1H-NMR spectra of EDY-B and EDY-C

    图  3  化合物EDY-A(红色)与对照组(黑色)的EPR谱图

    Figure  3.  EPR spectra of compound EDY-A (red) and control (black)

    图  4  在37 ℃下,化合物EDY-A(a)和EDY-C(b)与pUC19 DNA作用48 h后的凝胶电泳图(单位:mmol/L)

    Figure  4.  Gel electrophoresis of compound EDY-A (a) and EDY-C (b) reacting with pUC19 DNA at 37 ℃ for 48 h (unit: mmol/L)

    图  5  不同种类烯二炔化合物对牛血清白蛋白和溶菌酶的SDS-PAGE凝胶电泳图

    Figure  5.  SDS-PAGE gel electrophoresis of the different enediyne compounds on BSA and xysozyme

    (a) c/(mmol·L−1): lane 1~8: 0.1, 0.2, 0.5, 1, 2, 5, 10, 20; (b) c/(mmol·L−1): lane 9: EDY-A control group; Con: Protein control group. (c) c/(mmol·L−1): lane 1~5: 1, 2, 5, 10, 20;Con: Protein control group. (d) c/(mmol·L−1): lane 1~7: 1, 2, 5, 7.5, 10, 20, 40;lane 8: EDY-C control group; Con: Protein control group

  • [1] EDO K, MIZUGAKI M, KOIDE,Y, et al. The structure of neocarzinostatin chromophore possessing a novel bicyclo-[7, 3, 0]dodecadiyne system [J]. Tetrahedron Letters, 1985, 26 (3): 331-334.
    [2] JONES R R, BERGMAN R G. p-Benzyne generation as an intermediate in a thermal isomerization reaction and trapping evidence for the 1, 4-benzenediyl structure [J]. Journal of the American Chemical Society, 1972, 94 (2): 660-661.
    [3] BERGMAN R G. Reactive 1, 4-dehydroaromatics [J]. Accounts of Chemical Research, 1973, 6 (1): 25-31.
    [4] LEE M D, DUNNE T S, CHANG C C, et al. Calicheamicins, a novel family of antitumor antibiotics: 4. Structure elucidation of calicheamicins . Beta. 1Br, . Gamma. 1Br, . Alpha. 2I, . Alpha. 3I, . Beta. 1I, . Gamma. 1I, and . Delta. 1I [J]. Journal of the American Chemical Society, 1992, 114 (3): 985-997.
    [5] GOLIK J, CLARDY J, DUBAY G, et al. Esperamicins, a novel class of potent antitumor antibiotics: 2. Structure of esperamicin X [J]. Journal of the American Chemical Society, 1987, 109 (11): 3461-3462.
    [6] KONISHI M, OHKUMA H, TSUNO T, et al. Crystal and molecular structure of dynemicin A: A Novel 1, 5-diyn-3-ene antitumor antibiotic [J]. Journal of the American Chemical Society, 1990, 112 (9): 3715-3716.
    [7] KEN-ICHIRO Y, MINAMI Y, AZUMA R, et al. Structure and cycloaromatization of a novel enediyne, C-1027 chromophore [J]. Tetrahedron Letters, 1993, 34 (16): 2637-2640.
    [8] SMITH A L, NICOLAOU K. The enediyne antibiotics [J]. Journal of Medicinal Chemistry, 1996, 39 (11): 2103-2117.
    [9] SHEN B, HINDRA YAN X, et al. Enediynes: Exploration of microbial genomics to discover new anticancer drug leads [J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25 (1): 9-15.
    [10] BDOUR H M, ROY S, BASAK A. Proteins as alternate targets of enediynes [J]. Letters in Drug Design & Discovery, 2015, 12 (7): 545-557.
    [11] ZEIN N, SOLOMON W, CASAZZA A M, et al. Protein damage caused by a synthetic enediyne core [J]. Bioorganic & Medicinal Chemistry Letters, 1993, 3 (6): 1351-1356.
    [12] FOUAD F S, WRIGHT J M, PLOURDE G, et al. Synthesis and protein degradation capacity of photoactivated enediynes [J]. Journal of Organic Chemistry, 2005, 70 (24): 9789-9797.
    [13] PORTER M R, KOCHI A, KARTY J A, et al. Chelation-induced diradical formation as an approach to modulation of the amyloid-β aggregation pathway [J]. Chemical Science, 2015, 6 (2): 1018-1026.
    [14] KOGA N, MOROKUMA K. Comparison of biradical formation between enediyne and enyne-allene. Ab initio CASSCF and MRSDCI study [J]. Journal of the American Chemical Society, 1991, 113 (6): 1907-1911.
    [15] BASAK A, MANDAL S, BAG S S. Chelation-controlled Bergman cyclization: Synthesis and reactivity of enediynyl ligands [J]. Chemical Reviews, 2003, 103 (10): 4077-4094.
    [16] SUN S, ZHU C, SONG D, et al. Preparation of conjugated polyphenylenes from maleimide-based enediynes through thermal-triggered Bergman cyclization polymerization [J]. Polymer Chemistry, 2014, 5 (4): 1241-1247.
    [17] ZHANG M, LI B, CHEN H, et al. Triggering the antitumor activity of acyclic enediyne through maleimide-assisted rearrangement and cycloaromatization [J]. The Journal of organic chemistry. 2020, 85 (15): 9808-9819.
    [18] WANG W, LU H, ZHANG M, et al. Synthesis of maleimide-based enediynes with cyclopropane moieties for enhanced cytotoxicity under normoxic and hypoxic conditions [J]. Journal of Materials Chemistry B, 2021, 9 (22): 4502-4509.
    [19] ZOEPFL M, DWIVEDI R, TAYLOR M C, et al. Antiviral activities of four marine sulfated glycans against adenovirus and human cytomegalovirus [J]. Antiviral Research, 2021, 190: 105077.
    [20] MATHESON N J, LEHNER P J. How does SARS-CoV-2 cause COVID-19? [J]. Science, 2020, 369 (6503): 510-511.
    [21] ZHANG R, FENG X, ZHANG R, et al. Breaking parallel orientation of rods via a dendritic architecture toward diverse supramolecular structures [J]. Angewandte Chemie International Edition, 2019, 58 (34): 11879-11885.
    [22] O'BRIEN C J, KANTCHEV E A B, VALENTE C, et al. Easily prepared air- and moisture-stable Pd–NHC (NHC=N-Heterocyclic Carbene) complexes: A reliable, user-friendly, highly active palladium precatalyst for the Suzuki–Miyaura reaction [J]. Chemistry-a European Journal, 2006, 12 (18): 4743-4748.
    [23] DEORE P S, ARGADE N P. Sonogashira coupling reactions of bromomaleimides: Route to alkyne/cis-alkene/alkyl maleimides: synthesis of luffarin X and cacospongionolide C [J]. Journal of Organic Chemistry, 2012, 77 (1): 739-746.
    [24] JANZEN E G, BLACKBURN B J. Detection and identification of short-lived free radicals by an electron spin resonance trapping technique [J]. Journal of the American Chemical Society, 1968, 90 (21): 5909-5910.
    [25] KAR M, BASAK A. Design, synthesis, and biological activity of unnatural enediynes and related analogues equipped with pH-dependent or phototriggering devices [J]. Chemical Reviews, 2007, 107 (7): 2861-2890.
    [26] ZHANG M, LU H, LI B, et al. Experimental and computational study on the intramolecular hydrogen atom transfer reactions of maleimide-based enediynes after cycloaromatization [J]. The Journal of organic chemistry, 2021, 86 (2): 1549-1559.
  • 加载中
图(5)
计量
  • 文章访问数:  3
  • HTML全文浏览量:  3
  • PDF下载量:  0
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-05-30
  • 网络出版日期:  2022-06-28

目录

    /

    返回文章
    返回