留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

应中央军委要求,2022年9月起,《药学实践杂志》将更名为《药学实践与服务》,双月刊,正文96页;2023年1月起,拟出版月刊,正文64页,数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿!

胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用

邓宇晨 顾嘉伟 聂菲 肖良

邓宇晨, 顾嘉伟, 聂菲, 肖良. 胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用[J]. 药学实践与服务, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
引用本文: 邓宇晨, 顾嘉伟, 聂菲, 肖良. 胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用[J]. 药学实践与服务, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
Citation: DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001

胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用

doi: 10.3969/j.issn.1006-0111.2016.06.001
基金项目: 国家自然科学基金面上项目(81470518)

Cystine knot peptide's properties and its applications for drug design and molecular engineering

  • 摘要: 胱氨酸结(cystine knot,CK)模体是由两对二硫键及其相连的肽链骨架形成的一个内部环以及从环中穿过的第三对二硫键组成的球形结构,广泛存在于真菌、植物、海洋软体动物、昆虫以及蜘蛛等生物的毒素多肽和蛋白质中。CK多肽结构非常稳定、生物活性多样,是一类在药物设计和分子工程研究中的理想模型分子。本文综述了抑制剂胱氨酸结(inhibitor cystine knot,ICK)多肽和环形胱氨酸结(cyclic cystine knot,CCK)多肽两类主要CK毒素的氨基酸序列、拓扑结构、排列组合、人工合成以及空间折叠等特征,并进一步阐述了其在药物设计与分子工程中的应用前景。
  • [1] Mcdonald NQ, Hendrickson WA. A structural superfamily of growth factors containing a cystine knot motif[J]. Cell, 1993, 73(3):421-424.
    [2] Isaacs NW. Cystine knots[J]. Curr Opin Struct Biol, 1995, 5(3):391-395.
    [3] Park S, Stromstedt AA, Goransson U. Cyclotide structure-activity relationships:qualitative and quantitative approaches linking cytotoxic and anthelmintic activity to the clustering of physicochemical forces[J]. PLoS One, 2014, 9(3):e91430.
    [4] Reinwarth M, Nasu D, Kolmar H, et al. Chemical synthesis, backbone cyclization and oxidative folding of cystine-knot peptides:promising scaffolds for applications in drug design[J]. Molecules, 2012, 17(11):12533-12552.
    [5] Sato K, Yamaguchi Y, Ishida Y, et al. Roles of basic amino acid residues in the activity of μ-conotoxin GⅢA and GⅢB, peptide blockers of muscle sodium channels[J]. Chem Biol Drug Des, 2015, 85(4):488-493.
    [6] Green BR, Bulaj G, Norton RS. Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity[J]. Future Med Chem, 2014, 6(15):1677-1698.
    [7] Pallaghy PK, Norton RS,Nielsen KJ, et al. A common structural motif incorporating a cystine knot and a triple-stranded β-sheet in toxic and inhibitory polypeptides[J]. Protein Sci, 1994, 3(10):1833-1839.
    [8] Norton RS, Pallaghy PK. The cystine knot structure of ion channel toxins and related polypeptides[J]. Toxicon, 1998, 36(11):1573-1583.
    [9] Craik DJ, Daly NL, Waine C. The cystine knot motif in toxins and implications for drug design[J]. Toxicon, 2001, 39(1):43-60.
    [10] Schroeder CI, Nielsen KJ, Adams DA, et al. Effects of Lys2 to Ala2 substitutions on the structure and potency of ω-conotoxins MVⅡA and CVID[J]. Biopolymers, 2012, 98(4):345-356.
    [11] Almeida AM, Li R, Gellman SH. Parallel β-sheet secondary structure is stabilized and terminated by interstrand disulfide cross-linking[J]. J Am Chem Soc, 2012, 134(1):75-78.
    [12] Henriques ST, Huang YH, Chaousis S, et al. The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells[J]. Chem Biol, 2015, 22(8):1087-1097.
    [13] Skjeldal L, Gran L, Sletten K, et al. Refined structure and metal binding site of the kalata B1 peptide[J]. Arch Biochem Biophys, 2002, 399(2):142-148.
    [14] Ravipati AS, Henriques ST, Poth AG, et al. Lysine-rich cyclotides:a new subclass of circular knotted proteins from Violaceae[J]. ACS Chem Biol, 2015, 10(11):2491-2450.
    [15] Slazak B, Jacobsson E, Kuta E, et al. Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae)[J]. Phytochemistry, 2015, 117:527-536.
    [16] Reinwarth M, Glotzbach B, Tomaszowski M, et al. Oxidative folding of peptides with cystine-knot architectures:kinetic studies and optimization of folding conditions[J]. Chembiochem, 2013, 14(1):137-146.
    [17] Mao B. Topological chirality of proteins[J]. Protein Sci, 1993, 2(6):1057-1059.
    [18] Tang YQ, Yuan J, Osapay G, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins[J]. Science, 1999, 286(5439):498-502.
    [19] Kliemannel M, Weininger U, Balbach J, et al. Examination of the slow unfolding of pro-nerve growth factor argues against a loop threading mechanism for nerve growth factor[J]. Biochemistry, 2006, 45(11):3517-3524.
    [20] Daly NL, Craik DJ. Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1[J]. J Biol Chem, 2000, 275(25):19068-19075.
    [21] Olivera BM, Rivier J, Clark C, et al. Diversity of Conus neuropeptides[J]. Science, 1990, 249(4966):257-263.
    [22] Banerjee J, Gyanda R, Chang YP, et al. The chemical synthesis of alpha-conotoxins and structurally modified analogs with enhanced biological stability[J]. Methods Mol Biol, 2013, 1081:13-34.
    [23] Guo Y, Sun DM, Wang FL, et al. Diaminodiacid Bridges to Improve Folding and Tune the Bioactivity of Disulfide-Rich Peptides[J]. Angew Chem Int Ed Engl, 2015.
    [24] Cheneval O, Schroeder CI, Durek T, et al. Fmoc-based synthesis of disulfide-rich cyclic peptides[J]. J Org Chem, 2014, 79(12):5538-5544.
    [25] Poth AG, Colgrave ML, Philip R, et al. Discovery of cyclotides in the fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins[J]. ACS Chem Biol, 2011, 6(4):345-355.
    [26] Maciel IS, Azevedo VM, Pereira TC, et al. The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice[J]. Neuroscience, 2014, 277:794-805.
    [27] Datta A, Kundu P, Bhunia A. Designing potent antimicrobial peptides by disulphide linked dimerization and N-terminal lipidation to increase antimicrobial activity and membrane perturbation:Structural insights into lipopolysaccharide binding[J]. J Colloid Interface Sci, 2016, 461:335-345.
    [28] Ireland DC, Wang CK, Wilson JA, et al. Cyclotides as natural anti-HIV agents[J]. Biopolymers, 2008, 90(1):51-60.
    [29] Moore SJ, Leung CL, Norton HK, et al. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging[J]. PLoS One, 2013, 8(4):e60498.
  • [1] 杨媛媛, 安晓强, 许佳捷, 江键, 梁媛媛.  正极性驻极体联合5-氟尿嘧啶对瘢痕成纤维细胞生长抑制的协同作用 . 药学实践与服务, 2024, 42(6): 244-247. doi: 10.12206/j.issn.2097-2024.202310027
    [2] 岳春华, 贲永光, 王海桥.  基于NLRP1炎症小体探讨百合知母汤抗抑郁的作用机制 . 药学实践与服务, 2024, 42(8): 325-333. doi: 10.12206/j.issn.2097-2024.202401033
    [3] 李想, 陆鸿远, 张明玉, 高欢, 姚东, 许子华.  米格列醇激活UCP1介导棕色脂肪对冷暴露小鼠损伤的研究 . 药学实践与服务, 2024, 42(): 1-6. doi: 10.12206/j.issn.2097-2024.202404005
    [4] 刘汝雄, 杨万镇, 涂杰, 盛春泉.  铁死亡调控蛋白GPX4的小分子抑制剂研究进展 . 药学实践与服务, 2024, 42(9): 375-378. doi: 10.12206/j.issn.2097-2024.202312075
  • 加载中
计量
  • 文章访问数:  4363
  • HTML全文浏览量:  563
  • PDF下载量:  780
  • 被引次数: 0
出版历程
  • 收稿日期:  2015-10-30
  • 修回日期:  2016-04-26

胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用

doi: 10.3969/j.issn.1006-0111.2016.06.001
    基金项目:  国家自然科学基金面上项目(81470518)

摘要: 胱氨酸结(cystine knot,CK)模体是由两对二硫键及其相连的肽链骨架形成的一个内部环以及从环中穿过的第三对二硫键组成的球形结构,广泛存在于真菌、植物、海洋软体动物、昆虫以及蜘蛛等生物的毒素多肽和蛋白质中。CK多肽结构非常稳定、生物活性多样,是一类在药物设计和分子工程研究中的理想模型分子。本文综述了抑制剂胱氨酸结(inhibitor cystine knot,ICK)多肽和环形胱氨酸结(cyclic cystine knot,CCK)多肽两类主要CK毒素的氨基酸序列、拓扑结构、排列组合、人工合成以及空间折叠等特征,并进一步阐述了其在药物设计与分子工程中的应用前景。

English Abstract

邓宇晨, 顾嘉伟, 聂菲, 肖良. 胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用[J]. 药学实践与服务, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
引用本文: 邓宇晨, 顾嘉伟, 聂菲, 肖良. 胱氨酸结模体多肽的特征及其在药物设计和分子工程中的应用[J]. 药学实践与服务, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
Citation: DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001
参考文献 (29)

目录

    /

    返回文章
    返回