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多肽新药研发策略研究进展 被引量：7

Advances in the strategies for the development of novel peptide drugs
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摘要 多肽药物具有生物活性高、药用剂量小、产业化开发优势明显等诸多优点,已成为全球关注的创新药物研发热点之一.但是其代谢不稳定、半衰期短及较难通透组织屏障等缺点严重阻碍了多肽新药在临床治疗中的广泛应用.为了解决这些限制多肽药物的瓶颈,本课题组发展了一系列的改造策略.通过这些策略的应用,以期加快多肽药物临床应用的步伐.本文主要结合本课题组的工作对多肽新药创制过程中所遇到的关键问题及解决思路进行综述. The development of peptide drugs has become a global concern due to their merits such as high biological activity, low medicinal dose and easy to industrialization. However, low enzymatic stability, short half-life and low tissue permeability hamper the clinical application of nature peptide drugs. In order to overcome the bottlenecks, we developed a series of new modified strategies. By applications of these strategies, we wish to accelerate the pace of the development in clinical application of peptide drugs.
作者 张伟 宋竟婧 张邦治 杨雯乐 王锐
机构地区 甘肃省新药临床前研究省重点实验室
出处 《中国科学：化学》 CAS CSCD 北大核心 2013年第8期941-952,共12页 SCIENTIA SINICA Chimica
基金 国家自然科学基金项目(91213302,20932003,21272102) “重大新药创制”科技重大专项(2012ZX09504001-003) 长江学者和创新团队发展计划(IRT1137)的资助
关键词 多肽药物 神经肽 抗菌肽 靶向肽 穿膜肽 peptide drug neuropeptide antimicrobial peptide targeting peptide cell penetrating peptide
分类号 R914 [医药卫生—药物化学]
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参考文献79

  • 1Sewald N, Jakubke HD. Peptides: Chemistry and Biology. Weinheim: Wiley-VCH, 2002.
  • 2Sato AK, Viswanathan M, Kent RB, Wood CR. Therapeutic peptides: Technological advances driving peptides into development. Curr Opin Biotechnol, 2006, 17: 638-462.
  • 3Nestor JJ Jr. The medicinal chemistry of peptides. Curr Med Chem. 2009, 16: 4399-4418.
  • 4Jiang XX, Zhang YF, Chan ASC, Wang R. Highly enantioselective synthesis of γ-nitro heteroaromatic ketones in a double sterecontrolled manner catalyzed by bifunctional thiourea catalysts based on dehydroabietic amine: A double sterecontrolled approach to pyrrolidine carboxylic acids. Org Lett, 2009, 11: 153-156.
  • 5Zhang G, Zhang YH, Jiang XX, Yan WJ, Wang R. Highly enantioslective synthesis of multisubstituted polyfunctional dihydropyrrole via an organocatalytic tandem michael/cyclization sequence. Org Lett, 2011, 13: 3806-3809.
  • 6Jiang XX, Wang YQ, Zhang G, Fu D, Zhang FT, Kai M, Wang R. Enantioselective synthesis of cyclic thioureas via Mannich reaction and concise synthesis of highly optically active methylthioimidazolines: Discovery of a more potent antipyretic agent. Adv Synth Catal, 2011, 353: 1787-1796.
  • 7Jiang XX, Zhang YF, Wu LP, Zhang G, Liu X, Zhang HL, Fu D, Wang R. Doubly stereocontrolled asymmetric aza-Henry reaction with in situ generation of N-Boc imines catalyzed by novel rosin-derived amine thiourea catalysts. Adv Synth Catal, 2009, 351: 2096-2100.
  • 8Jiang XX, Zhang YF, Liu X, Zhang G, Lai LH, Wu LP, Zhang JN, Wang R. Enantio-and diastereoselective asymmetric addition of 1,3-dicarbonyl compounds to nitroalkenes in a doubly stereocontrolled manner catalyzed by bifunctional rosin-derived amine thiourea catalysts. J Org Chem, 2009, 74: 5562-5567.
  • 9Jiang XX, Fu D, Zhang G, Cao Y, Liu L, Song J, Wang R. Highly diastereo-and enantioselective Mannich reaction of lactones with N-Boc-aldimines catalyzed by bifunctional rosin-derived amine thiourea catalysts. Chem Commun, 2010, 46: 4294-4296.
  • 10Jiang XX, Zhang G, Fu D, Cao YM, Shen FF, Wang R. Direct organocatalytic asymmetric aldol reaction of R-isothiocyanato imides to R-ketoesters under low ligand loading: A doubly stereocontrolled approach to cyclic thiocarbamates bearing chiral quaternary stereocenters. Org Lett, 2010, 12: 1544-1547.

同被引文献126

  • 1方泉,张邦治,王锐.神经肽FF的构效关系研究[J].化学进展,2007,19(12):1977-1985. 被引量：2
  • 2Chanut-Delalande H, Hashimoto Y, Pelissier-Monier A, et al. Pri pep- tides are mediators of ecdysone for the temporal control of develop- ment[J]. Nat Cell Biol, 2014, 16(11): 1035-1044.
  • 3MiUar RP, Newton CL. Current and future applications of GnRH, kisspeptin and neurokinin B analogues[J]. Nat Rev Endocrinol, 2013, 9(8): 451-466.
  • 4Yang HY, Fratta W, Majane EA, et al. Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine[J]. Proc Natl Acad Sci U S A, 1985, 82(22): 7757-7761.
  • 5Bonini JA, Jones KA, Adham N, et al. Identification and characteriza- tion of two G protein-coupled receptors for neuropeptide FF[J]. J Biol Chem, 2000, 275(50): 39324-39331.
  • 6Liu Q, Guan XM, Martin WJ, et al. Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception [J]. J Biol Chem, 2001, 276(40): 36961-36969.
  • 7Gouarderes C, Quelven I, Mollereau C, et al. Quantitative autoradio- graphic distribution of NPFF1 neuropeptide FF receptor in the rat brain and comparison with NPFF2 receptor by using [125I]YVP and [ (125I]EYF as selective radioligands [J]. Neuroscience, 2002, 115(2): 349-361.
  • 8Zeng Z, McDonald TP, Wang R, et al. Neuropeptide FF receptor 2 (NPFF2) is localized to pain-processing regions in the primate spinal cord and the lower level of the medulla oblongata [J]. J Chem Neuroanat, 2003, 25(4): 269-278.
  • 9Goncharuk V, Zeng Z, Wang R, et al. Distribution of the neuropep- tide FF1 receptor (hFF 1) in the human hypothalamus and surrounding basal forebrain structures: immunohistochemical study [J]. J Comp Neurol, 2004, 474(4): 487-503.
  • 10Sundblom DM, Heikman P, Naukkarinen H, et al. Blood concentra- tions of vasopressin, neuropeptide FF and prolactin are increased by high-dose right unilateral ECT[J]. Peptides, 1999, 20(3): 319-326.

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中国科学：化学
2013年 第8期

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