FmocFDapPdChaWR | 1054631-99-0

• 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: FmocFDapPdChaWR
• 英文别名: Fmoc-Phe-Dap-Pro-D-Cha-Trp-Arg-OH；(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-3-amino-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenylpropanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-cyclohexylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
• CAS: 1054631-99-0
• 化学式: C₅₈H₇₁N₁₁O₉
• 分子量: 1066.27
• InChiKey: HYQMGHPULYGNHB-UGTGZNECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  78
• 可旋转键数：
  25
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  319
• 氢给体数：
  10
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  FmocFDapPdChaWR 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 FmocF
  参考文献：
  名称：

  Low-Molecular-Weight Peptidic and Cyclic Antagonists of the Receptor for the Complement Factor C5a

  摘要：

  Activation of the human complement system of plasma proteins during immunological host defense can result in overproduction of potent proinflammatory peptides such as the anaphylatoxin C5a. Excessive levels of C5a are associated with numerous immunoinflammatory diseases, but there is as yet no clinically available antagonist to regulate the effects of C5a. We now describe a series of small molecules derived from the C-terminus of C5a, some of which are the most potent low-molecular-weight C5a receptor antagonists reported to date for the human polymorphonuclear leukocyte (PMN) C5a receptor. H-1 NMR spectroscopy was used to determine solution structures for two cyclic antagonists and to indicate that antagonism is related to a turn conformation, which can be stabilized in cyclic molecules that are preorganized for receptor binding. While several cyclic derivatives were of similar antagonistic potency, the most potent antagonist was a hexapeptide-derived macrocycle AcF[OPdChaWR] with an IC50 = 20 nM against a maximal concentration of C5a (100 nM) on intact human PMNs. Such potent C5a antagonists may be useful probes to investigate the role of C5a in host defenses and to develop therapeutic agents for the treatment of many currently intractable inflammatory conditions.

  DOI：

  10.1021/jm9806594
• 作为产物：
  描述：

  BOC-L-脯氨酸 、 N-叔丁氧羰基-L-色氨酸 、 (S)-3-amino-2-tert-butoxycarbonylaminopropionic acid 、 N-BOC-3-环己基-D-丙氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 FmocFDapPdChaWR
  参考文献：
  名称：

  Low-Molecular-Weight Peptidic and Cyclic Antagonists of the Receptor for the Complement Factor C5a

  摘要：

  Activation of the human complement system of plasma proteins during immunological host defense can result in overproduction of potent proinflammatory peptides such as the anaphylatoxin C5a. Excessive levels of C5a are associated with numerous immunoinflammatory diseases, but there is as yet no clinically available antagonist to regulate the effects of C5a. We now describe a series of small molecules derived from the C-terminus of C5a, some of which are the most potent low-molecular-weight C5a receptor antagonists reported to date for the human polymorphonuclear leukocyte (PMN) C5a receptor. H-1 NMR spectroscopy was used to determine solution structures for two cyclic antagonists and to indicate that antagonism is related to a turn conformation, which can be stabilized in cyclic molecules that are preorganized for receptor binding. While several cyclic derivatives were of similar antagonistic potency, the most potent antagonist was a hexapeptide-derived macrocycle AcF[OPdChaWR] with an IC50 = 20 nM against a maximal concentration of C5a (100 nM) on intact human PMNs. Such potent C5a antagonists may be useful probes to investigate the role of C5a in host defenses and to develop therapeutic agents for the treatment of many currently intractable inflammatory conditions.

  DOI：

  10.1021/jm9806594

文献信息

• Low-Molecular-Weight Peptidic and Cyclic Antagonists of the Receptor for the Complement Factor C5a
  作者：Angela M. Finch、Allan K. Wong、Natalii J. Paczkowski、S. Khémar Wadi、David J. Craik、David P. Fairlie、Stephen M. Taylor

  DOI：10.1021/jm9806594

  日期：1999.6.1

  Activation of the human complement system of plasma proteins during immunological host defense can result in overproduction of potent proinflammatory peptides such as the anaphylatoxin C5a. Excessive levels of C5a are associated with numerous immunoinflammatory diseases, but there is as yet no clinically available antagonist to regulate the effects of C5a. We now describe a series of small molecules derived from the C-terminus of C5a, some of which are the most potent low-molecular-weight C5a receptor antagonists reported to date for the human polymorphonuclear leukocyte (PMN) C5a receptor. H-1 NMR spectroscopy was used to determine solution structures for two cyclic antagonists and to indicate that antagonism is related to a turn conformation, which can be stabilized in cyclic molecules that are preorganized for receptor binding. While several cyclic derivatives were of similar antagonistic potency, the most potent antagonist was a hexapeptide-derived macrocycle AcF[OPdChaWR] with an IC50 = 20 nM against a maximal concentration of C5a (100 nM) on intact human PMNs. Such potent C5a antagonists may be useful probes to investigate the role of C5a in host defenses and to develop therapeutic agents for the treatment of many currently intractable inflammatory conditions.