methyl acryloyl-L-alanyl-L-phenylalanine | 952312-44-6

• 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: methyl acryloyl-L-alanyl-L-phenylalanine
• CAS: 952312-44-6
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: NQHCBQVVYORNGE-AAEUAGOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.58
• 重原子数：
  22.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.5
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl acryloyl-L-alanyl-L-phenylalanine 、 3-(2',3',4',6'-tetra-O-benzyl-α-D-galactopyranosyl)prop-1-ene 在 substituted Grubbs-type ruthenium carbene complex 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以76%的产率得到methyl (2S)-3-phenyl-2-[[(2S)-2-[[(E)-4-[(2R,3S,4R,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]but-2-enoyl]amino]propanoyl]amino]propanoate
  参考文献：
  名称：

  Cross‐metathesis ofC‐Glycosides and Peptides

  摘要：

  Peptides bearing an acryloyl residue at their N-terminus were coupled with various C-glycosides in an equimolar ratio via cross-metathesis. The newly formed olefin was obtained with high E/Z selectivity in satisfying to high yields with low homodimerization of the starting materials. The posttranslational cross-metathesis approach was shown to be suitable for the combinatorial synthesis of a small library of C-glycopeptides.

  DOI：

  10.1080/00397910701481146
• 作为产物：
  描述：

  L-丙氨酰-L-苯丙氨酸 在 盐酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl acryloyl-L-alanyl-L-phenylalanine
  参考文献：
  名称：

  Cross‐metathesis ofC‐Glycosides and Peptides

  摘要：

  Peptides bearing an acryloyl residue at their N-terminus were coupled with various C-glycosides in an equimolar ratio via cross-metathesis. The newly formed olefin was obtained with high E/Z selectivity in satisfying to high yields with low homodimerization of the starting materials. The posttranslational cross-metathesis approach was shown to be suitable for the combinatorial synthesis of a small library of C-glycopeptides.

  DOI：

  10.1080/00397910701481146

文献信息

• Controlling Amphiphilic Polymer Folding beyond the Primary Structure with Protein-Mimetic Di(Phenylalanine)
  作者：Jacqueline L. Warren、Peter A. Dykeman-Bermingham、Abigail S. Knight

  DOI：10.1021/jacs.1c05659

  日期：2021.8.25

  functionality pales in comparison to natural biopolymers–strategies are limited for building the intricate network of noncovalent interactions necessary to elicit complex, protein-like functions. Using a bioinspired di(phenylalanine) acrylamide (FF) monomer, we explored the impact of various noncovalent interactions in generating ordered assembled structures. Amphiphilic copolymers were synthesized that

  虽然聚合物合成方法已经激增，但与天然生物聚合物相比，它们的功能相形见绌——构建复杂的非共价相互作用网络的策略是有限的，这些网络是引发复杂的、类蛋白质功能所必需的。我们使用受生物启发的二（苯丙氨酸）丙烯酰胺 (FF) 单体，探讨了各种非共价相互作用对生成有序组装结构的影响。合成的两亲共聚物在水性环境中坍缩成单链组件时表现出类似 β-折叠的局部结构。对一系列两亲共聚物的系统分析表明，整体崩溃主要是由疏水力驱动的。氢键和芳香相互作用稳定局部结构，因为通过圆二色性和硫黄素 T 荧光鉴定了 β-折叠样相互作用。对苯丙氨酸 (F) 和丙氨酸-苯丙氨酸丙烯酰胺 (AF) 共聚物的类似分析发现，将芳香族残基与聚合物主链分开足以诱导类似于 FF 共聚物的 β-折叠状局部结构；然而，AF 亚基之间的相互作用不如 FF 形成的相互作用稳定。此外，提供氢键的亲水性单体破坏了 FF 在折叠组件中形成的内部结构。总的
• The S1′–S3′ Pocket of the SARS‐CoV‐2 Main Protease Is Critical for Substrate Selectivity and Can Be Targeted with Covalent Inhibitors
  作者：Ming Liu、Jihui Li、Wenqi Liu、Ying Yang、Manman Zhang、Yuxin Ye、Wenning Zhu、Cuiyan Zhou、Hongbin Zhai、Zhengshuang Xu、Guoliang Zhang、Hao Huang

  DOI：10.1002/anie.202309657

  日期：2023.10.9

  The main protease (M^pro) of SARS‐CoV‐2 is a well‐characterized target for antiviral drug discovery. To date, most antiviral drug discovery efforts have focused on the S4–S1′ pocket of M^pro; however, it is still unclear whether the S1′–S3′ pocket per se can serve as a new site for drug discovery. In this study, the S1′–S3′ pocket of M^pro was found to differentially recognize viral peptidyl substrates. For instance, S3′ in M^pro strongly favors Phe or Trp, and S1′ favors Ala. The peptidyl inhibitor D‐4–77, which possesses an α‐bromoacetamide warhead, was discovered to be a promising inhibitor of M^pro, with an IC₅₀ of 0.95 μM and an antiviral EC₅₀ of 0.49 μM. The M^pro/inhibitor co‐crystal structure confirmed the binding mode of the inhibitor to the S1′–S3′ pocket and revealed a covalent mechanism. In addition, D‐4–77 functions as an immune protectant and suppresses SARS‐CoV‐2 M^pro‐induced antagonism of the host NF‐κB innate immune response. These findings indicate that the S1′–S3′ pocket of SARS‐CoV‐2 M^pro is druggable, and that inhibiting SARS‐CoV‐2 M^pro can simultaneously protect human innate immunity and inhibit virion assembly.

  摘要 SARS-CoV-2的主要蛋白酶（Mpro）是抗病毒药物发现的一个特征明确的靶点。迄今为止，大多数抗病毒药物的发现工作都集中在Mpro的S4-S1′口袋上；然而，S1′-S3′口袋本身能否作为药物发现的新靶点尚不清楚。本研究发现，Mpro的S1′-S3′口袋可以识别不同的病毒肽基底物。例如，Mpro 的 S3′ 极其偏爱 Phe 或 Trp，而 S1′ 则偏爱 Ala。肽基抑制剂 D-4-77 具有α-溴乙酰胺弹头，是一种很有前途的 Mpro 抑制剂，其 IC50 值为 0.95 μM，抗病毒 EC50 值为 0.49 μM。Mpro 与抑制剂的共晶体结构证实了抑制剂与 S1′-S3′ 口袋的结合模式，并揭示了共价机制。此外，D-4-77还具有免疫保护剂的功能，可抑制SARS-CoV-2 Mpro诱导的宿主NF-κB先天免疫反应的拮抗作用。这些研究结果表明，SARS-CoV-2 Mpro的S1′-S3′口袋是可药用的，抑制SARS-CoV-2 Mpro可同时保护人类先天免疫和抑制病毒组装。