N-(diethylphosphoryl)-L-isoleucyl-L-alanylglycyl-L-glutamyl-L-arginylglycine | 122924-13-4

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: N-(diethylphosphoryl)-L-isoleucyl-L-alanylglycyl-L-glutamyl-L-arginylglycine
• CAS: 122924-13-4
• 化学式: C₂₈H₅₂N₉O₁₂P
• 分子量: 737.748
• InChiKey: WWKQOUQGEPPGEM-QUVRYOLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.91
• 重原子数：
  50.0
• 可旋转键数：
  26.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  329.56
• 氢给体数：
  11.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-(diethylphosphoryl)-L-isoleucyl-L-alanylglycyl-L-glutamyl-L-arginylglycine 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 9.0h， 以16%的产率得到(7R,10R,19S)-2,7,10,16,16,19,21-heptamethyl-10-(3-methylbut-3-en-1-yl)-9,12,15,18,21-pentamethylene-7-(5-methylhexa-1,5-dien-2-yl)-19-(tert-pentyl)-21l5-tetracos-1-ene
  参考文献：
  名称：

  Phosphoramidate peptide inhibitors of human skin fibroblast collagenase

  摘要：

  An extensive series of N-(monoethylphosphoryl)peptides was synthesized and their inhibition of purified human skin fibroblast collagenase examined. At the cleavage site S1 all reported compounds have the (EtO)(OK)P(O) group and the peptide side chain extended toward the C-terminal end (up to P5') of the substrate sequence. These phosphoramidates with a tetrahedrally hybridized phosphorus atom are thought to be transition state analogue inhibitors. They exhibited fair inhibitory potency against this vertebrate collagenase having Ki values in the micromolar range. The most potent of these, (EtO)(OK)P(O)-Ile-TrpNHCH3 (68), inhibits with a Ki value of 1.5 microM and is nearly 100 times stronger than (EtO)(OK)P(O)-Ile-Ala-GlyOK (51) (Ki of 140 microM), which has the sequence matching that of the alpha 1 (I) chain of collagen in P1', P2', P3' after the cleavage site. Several compounds were prepared in an attempt to identify the nature of the S2', S3', and S4' binding sites. Alanine at the P2' position was replaced by leucine, phenylalanine, tryptophan, or tyrosine derivatives, resulting in Ki values in a significantly lower range, 1.0-40 microM, compared to 51. No upper size limitation or specificity has been found at this position, yet similar replacements at the P3' position, which is occupied naturally by a glycine residue, gave weaker inhibitors: (EtO)(OK)P(O)-Ile-Tyr(OBzl)-PheOK (57) had a Ki of 120 microM. Hexapeptide derivatives had weaker activities in the 270 microM-2 mM range. All inhibitors were evaluated by using the synthetic thio peptolide spectrophotometric assay.

  DOI：

  10.1021/jm00163a044
• 作为产物：
  描述：

  {(S)-2-[(2S,3S)-2-(Diethoxy-phosphorylamino)-3-methyl-pentanoylamino]-propionylamino}-acetic acid benzyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 N-(diethylphosphoryl)-L-isoleucyl-L-alanylglycyl-L-glutamyl-L-arginylglycine
  参考文献：
  名称：

  Phosphoramidate peptide inhibitors of human skin fibroblast collagenase

  摘要：

  An extensive series of N-(monoethylphosphoryl)peptides was synthesized and their inhibition of purified human skin fibroblast collagenase examined. At the cleavage site S1 all reported compounds have the (EtO)(OK)P(O) group and the peptide side chain extended toward the C-terminal end (up to P5') of the substrate sequence. These phosphoramidates with a tetrahedrally hybridized phosphorus atom are thought to be transition state analogue inhibitors. They exhibited fair inhibitory potency against this vertebrate collagenase having Ki values in the micromolar range. The most potent of these, (EtO)(OK)P(O)-Ile-TrpNHCH3 (68), inhibits with a Ki value of 1.5 microM and is nearly 100 times stronger than (EtO)(OK)P(O)-Ile-Ala-GlyOK (51) (Ki of 140 microM), which has the sequence matching that of the alpha 1 (I) chain of collagen in P1', P2', P3' after the cleavage site. Several compounds were prepared in an attempt to identify the nature of the S2', S3', and S4' binding sites. Alanine at the P2' position was replaced by leucine, phenylalanine, tryptophan, or tyrosine derivatives, resulting in Ki values in a significantly lower range, 1.0-40 microM, compared to 51. No upper size limitation or specificity has been found at this position, yet similar replacements at the P3' position, which is occupied naturally by a glycine residue, gave weaker inhibitors: (EtO)(OK)P(O)-Ile-Tyr(OBzl)-PheOK (57) had a Ki of 120 microM. Hexapeptide derivatives had weaker activities in the 270 microM-2 mM range. All inhibitors were evaluated by using the synthetic thio peptolide spectrophotometric assay.

  DOI：

  10.1021/jm00163a044