(2S,3S)-N2-(2-((S)-2-carbamoylpyrrolidin-1-yl)-2-oxoethyl)-N3-((S)-1-((4-guanidinobutyl)amino)-4-methyl-1-oxopentan-2-yl)oxirane-2,3-dicarboxamide | 1392424-20-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S)-N2-(2-((S)-2-carbamoylpyrrolidin-1-yl)-2-oxoethyl)-N3-((S)-1-((4-guanidinobutyl)amino)-4-methyl-1-oxopentan-2-yl)oxirane-2,3-dicarboxamide
• CAS: 1392424-20-2
• 化学式: C₂₂H₃₈N₈O₆
• 分子量: 510.594
• InChiKey: JBHFPXMTOYQFJW-OTRWWLKZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.74
• 重原子数：
  36.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  225.13
• 氢给体数：
  7.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  维达列汀杂质44 、 N-(反式-环氧丁二酰基)-L-亮氨酸-4-胍基丁基酰胺 在 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 生成 (2S,3S)-N2-(2-((S)-2-carbamoylpyrrolidin-1-yl)-2-oxoethyl)-N3-((S)-1-((4-guanidinobutyl)amino)-4-methyl-1-oxopentan-2-yl)oxirane-2,3-dicarboxamide
  参考文献：
  名称：

  Foot and mouth disease leader protease (Lbpro): Investigation of prime side specificity allows the synthesis of a potent inhibitor

  摘要：

  Foot and mouth disease virus expresses its genetic information as a single polyprotein that is translated from the single-stranded RNA genome. Proteinases contained within the polyprotein then generate the mature viral proteins. The leader protease (Lb(pro)) performs the initial cleavage by freeing itself from the growing polypeptide chain; subsequently, Lb(pro) cleaves the two homologues of the host cell protein eukaryotic initiation factor 4G (eIF4G). We showed that Lb(pro) possesses specific binding sites at the non prime side from S-1 down to S-7 [Santos et al. (2009) Biochemistry, 48, 7948-7958]. Here, we demonstrate that Lb(pro) has high prime side specificity at least down to the S-5' site. Lb(pro) is thus not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It can still however cleave between both K down arrow G and G down arrow R pairs. We further determined the two-step irreversible inhibition (E + I <-> EI -> E - I) kinetic parameters of two known irreversible epoxide-based inhibitors of cysteine proteinases, E64 and CA074 on Lb(pro) that show for the reversible step (E + I <-> EI) K-i = 3.4 mu M and 11.6 mu M, and for the irreversible step (EI -> E-I) k(4) = 0.16 and 0.06 min(-1), respectively. Knowledge of the Lb(pro) specificity led us to extend E64 by addition of the dipeptide R-P. This compound, termed E64-R-P-NH2, irreversibly inhibited Lb(pro) with a K-i = 30 nM and k(4) = 0.01 min(-1) and can serve as the basis for design of specific inhibitors of FMDV replication. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biochi.2011.10.016