Fmoc-O-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-L-serine | 1101193-41-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-O-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-L-serine
• 英文别名: (2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 1101193-41-2
• 化学式: C₂₄H₂₈N₄O₇
• 分子量: 484.509
• InChiKey: YTHKPQSMRZQREU-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  35.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  152.08
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  O-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-L-serine 、 氯甲酸-9-芴基甲酯 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 以1.26 g的产率得到Fmoc-O-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-L-serine
  参考文献：
  名称：

  Tyrosine-sulfate isosteres of CCR5 N-terminus as tools for studying HIV-1 entry

  摘要：

  The HIV-1 co-receptor CCR5 possesses sulfo-tyrosine (TYS) residues at its N-terminus (Nt) that are required for binding HIV-1 gp120 and mediating viral entry. By using a 14-residue fragment of CCR5 Nt containing two TYS residues, we recently showed that CCR5 Nt binds gp120 through a conserved region specific for TYS moieties and suggested that this site may represent a target for inhibitors and probes of HIV-1 entry. As peptides containing sulfo-tyrosines are difficult to synthesize and handle due to limited stability of the sulfo-ester moiety, we have now incorporated TYS isosteres into CCR5 Nt analogs and assessed their binding to a complex of gp120-CD4 using saturation transfer difference (STD) NMR and surface plasmon resonance (SPR). STD enhancements for CCR5 Nt peptides containing tyrosine sulfonate (TYSN) in complex with gp120-CD4 were very similar to those observed for sulfated CCR5 Nt peptides indicating comparable modes of binding. STD enhancements for phosphotyrosine-containing CCR5 Nt analogs were greatly diminished consistent with earlier findings showing sulfo-tyrosine to be essential for CCR5 Nt binding to gp120. Tyrosine sulfonate-containing CCR5 peptides exhibited reduced water solubility, limiting their use in assay and probe development. To improve solubility, we designed, synthesized, and incorporated in CCR5 Nt peptide analogs an orthogonally functionalized azido tris(ethylenoxy) L-alanine (L-ate-Ala) residue. Through NMR and SPR experiments, we show a 19-residue TYSN-containing peptide to be a functional, hydrolytically stable CCR5 Nt isostere that was in turn used to develop both SPR-based and ELISA assays to screen for inhibitors of CCR5 binding to gp120-CD4. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.10.005

文献信息

• STAPLED TRIAZOLE CO-AGONISTS OF THE GLUCAGON AND GLP-1 RECEPTORS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：EP3842061A1

  公开（公告）日：2021-06-30

  ABSTRACT OF THE DISCLOSURE The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

  公开内容摘要 本发明的钉钉肽及其药学上可接受的盐类是胰高血糖素受体和 GLP-1 受体的共拮抗剂，可用于治疗、预防和抑制由胰高血糖素受体和 GLP-1 受体介导的疾病，包括但不限于糖尿病、非酒精性脂肪肝（NAFLD）、非酒精性脂肪性肝炎（NASH）和肥胖症等代谢性疾病。
• [EN] STAPLED TRIAZOLE CO-AGONISTS OF THE GLUCAGON AND GLP-1 RECEPTORS<br/>[FR] CO-AGONISTES TRIAZOLE AGRAFÉS DE RÉCEPTEURS DU GLUCAGON ET DU GLP-1
  申请人：MERCK SHARP & DOHME

  公开号：WO2021133644A1

  公开（公告）日：2021-07-01

  The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.