(2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-(3-non-2-ynylsulfonylpropylamino)-3-oxopropyl]butanamide | 1441770-09-7

• 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: (2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-(3-non-2-ynylsulfonylpropylamino)-3-oxopropyl]butanamide
• CAS: 1441770-09-7
• 化学式: C₂₁H₃₈N₂O₆S
• 分子量: 446.609
• InChiKey: CSAGZHVXBISHJZ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-壬烯-1-醇 在 盐酸 、 N-氯代丁二酰亚胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三苯基膦 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 (2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-(3-non-2-ynylsulfonylpropylamino)-3-oxopropyl]butanamide
  参考文献：
  名称：

  Sulfonyl 3-Alkynyl Pantetheinamides as Mechanism-Based Cross-Linkers of Acyl Carrier Protein Dehydratase

  摘要：

  Acyl carrier proteins (ACPs) play a central role in acetate biosynthetic pathways, serving as tethers for substrates and growing intermediates. Activity and structural studies have highlighted the complexities of this role, and the protein-protein interactions of ACPs have recently come under scrutiny as a regulator of catalysis. As existing methods to interrogate these interactions have fallen short, we have sought to develop new tools to aid their study. Here we describe the design, synthesis, and application of pantetheinamides that can cross-link ACPs with catalytic beta-hydroxy-ACP dehydratase (DH) domains by means of a 3-alkynyl sulfone warhead. We demonstrate this process by application to the Escherichia coli fatty acid synthase and apply it to probe protein-protein interactions with noncognate carrier proteins. Finally, we use solution-phase protein NMR spectroscopy to demonstrate that sulfonyl 3-alkynyl pantetheinamide is fully sequestered by the ACP, indicating that the crypto-ACP closely mimics the natural DH substrate. This cross-linking technology offers immediate potential to lock these biosynthetic enzymes in their native binding states by providing access to mechanistically cross-linked enzyme complexes, presenting a solution to ongoing structural challenges.

  DOI：

  10.1021/ja4042059