myelin basic protein (87 - 99)

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: myelin basic protein (87 - 99)
• 英文别名: MBP(87-99)；VHFFKNIVTPRTP；val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro；Myelin Basic Protein (87-99) (human, bovine, rat)；(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carboxylic acid
• 化学式: C₇₄H₁₁₄N₂₀O₁₇
• 分子量: 1555.84
• InChiKey: XSSZRUKIAIQNAZ-SAKFXWCOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  111
• 可旋转键数：
  45
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  598
• 氢给体数：
  19
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  myelin basic protein (87 - 99) 、 亚乙基丙二酸二乙酯 在 riboflavin tetrabutyrate 作用下， 以 甘油 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  脱羧烷基化通过氧化电位对天然蛋白质进行位点选择性生物缀合

  摘要：

  抗体-药物偶联物作为药物的出现推动了对提供均质加合物的可靠的定点选择性蛋白质修饰方法的需求。尽管使用工程氨基酸的生物正交方法通常为选择性功能化问题提供了一个优雅的解决方案，但是使用天然氨基酸实现均质性仍然是一个挑战。在这里，我们探索可见光介导的单电子转移，作为实现位点和化学选择性生物共轭的一种机制。具体来说，我们证明了使用光氧化还原催化作为选择性的平台，其中内部和C端羧酸盐之间的氧化电位差异可以用来专门获得C端功能化。这种氧化电位门控技术适用于内源肽，并已在蛋白质胰岛素上成功证明。作为一种基本的生物偶联新方法，该方法为光氧化还原催化的发展提供了一个蓝图，该氧化还原作为靶向其他氧化还原活性侧链进行天然偶联的通用平台。

  DOI：

  10.1038/nchem.2888
• 作为产物：
  描述：

  在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 myelin basic protein (87 - 99)
  参考文献：
  名称：

  US2016/95935

  摘要：

  公开号：

文献信息

• Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis
  作者：George Deraos、Maria Rodi、Hubert Kalbacher、Kokona Chatzantoni、Fotios Karagiannis、Loukas Synodinos、Panayiotis Plotas、Apostolos Papalois、Nikolaos Dimisianos、Panagiotis Papathanasopoulos、Dimitrios Gatos、Theodore Tselios、Vasso Apostolopoulos、Athanasia Mouzaki、John Matsoukas

  DOI：10.1016/j.ejmech.2015.06.015

  日期：2015.8

  Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-gamma, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation, rendering cyclo(87-99)(Ala91,Ala96)MBP87-99 an important candidate drug for MS immunotherapy. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials
  作者：Steven Bloom、Chun Liu、Dominik K. Kölmel、Jennifer X. Qiao、Yong Zhang、Michael A. Poss、William R. Ewing、David W. C. MacMillan

  DOI：10.1038/nchem.2888

  日期：2018.2.1

  advent of antibody–drug conjugates as pharmaceuticals has fuelled a need for reliable methods of site-selective protein modification that furnish homogeneous adducts. Although bioorthogonal methods that use engineered amino acids often provide an elegant solution to the question of selective functionalization, achieving homogeneity using native amino acids remains a challenge. Here, we explore visible-light-mediated

  抗体-药物偶联物作为药物的出现推动了对提供均质加合物的可靠的定点选择性蛋白质修饰方法的需求。尽管使用工程氨基酸的生物正交方法通常为选择性功能化问题提供了一个优雅的解决方案，但是使用天然氨基酸实现均质性仍然是一个挑战。在这里，我们探索可见光介导的单电子转移，作为实现位点和化学选择性生物共轭的一种机制。具体来说，我们证明了使用光氧化还原催化作为选择性的平台，其中内部和C端羧酸盐之间的氧化电位差异可以用来专门获得C端功能化。这种氧化电位门控技术适用于内源肽，并已在蛋白质胰岛素上成功证明。作为一种基本的生物偶联新方法，该方法为光氧化还原催化的发展提供了一个蓝图，该氧化还原作为靶向其他氧化还原活性侧链进行天然偶联的通用平台。
• US2016/95935
  申请人：——

  公开号：——

  公开（公告）日：——