H-Arg(MBS)-OH | 59052-83-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: H-Arg(MBS)-OH
• 英文别名: (2S)-2-amino-5-[[amino-[(4-methoxyphenyl)sulfonylamino]methylidene]amino]pentanoic Acid
• CAS: 59052-83-4
• 化学式: C₁₃H₂₀N₄O₅S
• 分子量: 344.392
• InChiKey: DCTOTIRHYVFLFF-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  氯甲酸-9-芴基甲酯 、 H-Arg(MBS)-OH 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 生成 N^α-(9-fluorenylmethyloxycarbonyl)-p-methoxybenzenesulfonyl-L-arginine
  参考文献：
  名称：

  The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease

  摘要：

  A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 Angstrom with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N-G-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00078-3
• 作为产物：
  描述：

  N-苄氧羰基-L-精氨酸 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 26.0h， 生成 H-Arg(MBS)-OH
  参考文献：
  名称：

  The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease

  摘要：

  A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 Angstrom with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N-G-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00078-3

文献信息

• The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease
  作者：Earl E Rutenber、James J De Voss、Lucas Hoffman、Robert M Stroud、Kwan H Lee、Juan Alvarez、Fiona McPhee、Charles Craik、Paul R Ortiz de Montellano

  DOI：10.1016/s0968-0896(97)00078-3

  日期：1997.7

  A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 Angstrom with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N-G-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors. (C) 1997 Elsevier Science Ltd.