N-Fmoc-N-methyl-D-serine

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-Fmoc-N-methyl-D-serine
• 英文别名: 2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-3-hydroxypropanoic acid
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.4
• InChiKey: ZVWHTEOKMWNXGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• CYCLIC PEPTIDE COMPOUND HAVING HIGH MEMBRANE PERMEABILITY, AND LIBRARY CONTAINING SAME
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP3636807A1

  公开（公告）日：2020-04-15

  The present inventors have found that when screening for cyclic peptide compounds that can specifically bind to a target molecule, the use of a library including cyclic peptide compounds having a long side chain in the cyclic portion can improve the hit rate for cyclic peptide compounds that can specifically bind to the target molecule. Meanwhile, the present inventors have found that tryptophan and tyrosine residues, which have conventionally been used in oral low molecular-weight pharmaceuticals and are amino acid residues having an indole skeleton or a hydroxyphenyl group, are not suitable for peptides intended to attain high membrane permeability.

  本发明人发现，在筛选能与目标分子特异性结合的环肽化合物时，使用包括环状部分具有长侧链的环肽化合物库，可以提高能与目标分子特异性结合的环肽化合物的命中率。同时，本发明者发现色氨酸和酪氨酸残基不适合用于旨在获得高膜渗透性的肽，这两种残基通常用于口服低分子量药物，是具有吲哚骨架或羟基苯基的氨基酸残基。
• METHOD FOR SYNTHESIZING PEPTIDE CONTAINING N-SUBSTITUTED AMINO ACID
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP3636656A1

  公开（公告）日：2020-04-15

  Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

  生产含有本发明的N-取代氨基酸或N-取代氨基酸类似物的多肽的方法包括以下步骤： 制备 Fmoc 保护的氨基酸、Fmoc 保护的氨基酸类似物或 Fmoc 保护的肽； 使用碱对具有 Fmoc 骨架的 Fmoc 保护氨基酸的保护基进行脱保护；以及 通过添加新的 Fmoc 保护氨基酸形成酰胺键； 当采用固相法生产多肽时，在酸性比反式脂肪酸弱的条件下从固相中裂解得到多肽。此外，所得多肽的至少一个侧链具有保护基团，该保护基团在碱性条件下未被脱保护，而在酸性弱于 TFA 的条件下被脱保护。