RR-beta-homoleucine-N-methylphenylalanine-NH2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: RR-beta-homoleucine-N-methylphenylalanine-NH2
• 英文别名: H-Arg-Arg-bAla(3S-iBu)-N(Me)Phe-NH2；(3S)-3-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-N,5-dimethylhexanamide
• 化学式: C₂₉H₅₁N₁₁O₄
• 分子量: 617.795
• InChiKey: AUFCDCQAZHQIQO-MLCQCVOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  44
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  276
• 氢给体数：
  8
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(9-芴甲氧羰酰基)-N-甲基-L-苯丙氨酸 、 FMOC-L-精氨酸 、 芴甲氧羰基-L-β-高亮氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 RR-beta-homoleucine-N-methylphenylalanine-NH2
  参考文献：
  名称：

  Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity

  摘要：

  The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structureactivity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of proteinprotein interactions into pharmaceutically relevant compounds. As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.

  DOI：

  10.1021/jm5015023

文献信息

• Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity
  作者：Padmavathy Nandha Premnath、Sandra N. Craig、Shu Liu、Erin L. Anderson、Asterios I. Grigoroudis、George Kontopidis、Tracy L. Perkins、Michael D. Wyatt、Douglas L. Pittman、Campbell McInnes

  DOI：10.1021/jm5015023

  日期：2015.1.8

  The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structureactivity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of proteinprotein interactions into pharmaceutically relevant compounds. As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.