PR73

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: PR73
• 英文别名: 2-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[2-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-4-[[6-[(2-amino-2-oxoethyl)-[2-(hexadecylamino)-2-oxoethyl]amino]-6-oxohexyl]amino]-4-oxo-1-phenylbutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]acetic acid
• 化学式: C₈₆H₁₃₃N₂₁O₁₅S
• 分子量: 1733.2
• InChiKey: OHCVZUDHUPRKEX-QOBKMEBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  123
• 可旋转键数：
  63
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  574
• 氢给体数：
  19
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  PR73 、 丁炔二酸 在 N-甲基吗啉 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.42h， 生成
  参考文献：
  名称：

  Thiol-derivatized minihepcidins retain biological activity

  摘要：

  Minihepcidins are small peptides that mimic biological activity of the iron-regulatory hormone hepcidin. Structurally, they contain thiol-free-cysteine residue in position 7 which is crucial for their bioactivity. Nonetheless, free sulfhydryl group is not desirable in pharmaceutical entities as it may lead to dermatological side effects. Moreover free thiol moiety is quite reactive and depending on conditions/reagents may be alkylated and/or oxidized giving various Cys-derivatives: S-alkyl cysteines, sulfoxides, sulfones, disulfides, cysteinesulfinic and cysteic acids. To limit such reactivity and maintain bioactivity of minihepcidin(s) we used thiol-protection strategy based on activated vinyl thioethers. Novel S-protected analogs of physiologically active minihepcidin PR73 were synthesized and tested in vitro showing activity comparable to parental molecule. The most active compound, PR73SH was also tested in vivo showing activity profile analogous to PR73. Collectively, our findings suggest that S-vinyl-derivatization of minihepcidin( s) may be a suitable approach in the development of physiologically active agonists of hepcidin. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.094

文献信息

• [EN] S-Alkylated Hepcidin Peptides and Methods of Making and Using Thereof<br/>[FR] PEPTIDES HEPCIDINE S-ALKYLÉS ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2016109363A1

  公开（公告）日：2016-07-07

  Disclosed herein S-alkylated hepcidin peptides and methods of making and using thereof. In some embodiments, the present invention is directed to an S-alkylated hepcidin peptide having the following Structural Formula IA or IB. In some embodiments, the present invention is directed to a composition comprising at least one S-alkylated hepcidin peptide of the present invention. In some embodiments, the present invention is directed to a method of binding a ferroportin or inducing ferroportin internalization and degradation which comprises contacting the ferroportin with at least one S-alkylated hepcidin peptide of the present invention. In some embodiments, the present invention is directed to a kit comprising at least one S-alkylated hepcidin peptide.

  本公开涉及S-烷基化肝铁蛋白肽及其制备和使用方法。在某些实施例中，本发明涉及具有以下结构式IA或IB的S-烷基化肝铁蛋白肽。在某些实施例中，本发明涉及包含至少一种本发明的S-烷基化肝铁蛋白肽的组合物。在某些实施例中，本发明涉及一种结合铁转运蛋白或诱导铁转运蛋白内化和降解的方法，该方法包括将铁转运蛋白与至少一种本发明的S-烷基化肝铁蛋白肽接触。在某些实施例中，本发明涉及一种包含至少一种S-烷基化肝铁蛋白肽的试剂盒。
• Thiol-derivatized minihepcidins retain biological activity
  作者：Eileen Fung、Kristine Chua、Tomas Ganz、Elizabeta Nemeth、Piotr Ruchala

  DOI：10.1016/j.bmcl.2014.12.094

  日期：2015.2

  Minihepcidins are small peptides that mimic biological activity of the iron-regulatory hormone hepcidin. Structurally, they contain thiol-free-cysteine residue in position 7 which is crucial for their bioactivity. Nonetheless, free sulfhydryl group is not desirable in pharmaceutical entities as it may lead to dermatological side effects. Moreover free thiol moiety is quite reactive and depending on conditions/reagents may be alkylated and/or oxidized giving various Cys-derivatives: S-alkyl cysteines, sulfoxides, sulfones, disulfides, cysteinesulfinic and cysteic acids. To limit such reactivity and maintain bioactivity of minihepcidin(s) we used thiol-protection strategy based on activated vinyl thioethers. Novel S-protected analogs of physiologically active minihepcidin PR73 were synthesized and tested in vitro showing activity comparable to parental molecule. The most active compound, PR73SH was also tested in vivo showing activity profile analogous to PR73. Collectively, our findings suggest that S-vinyl-derivatization of minihepcidin( s) may be a suitable approach in the development of physiologically active agonists of hepcidin. (C) 2015 Elsevier Ltd. All rights reserved.