Boc-Leu-Phe-NHBn | 184956-19-2

• 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: Boc-Leu-Phe-NHBn
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-(benzylamino)-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 184956-19-2
• 化学式: C₂₇H₃₇N₃O₄
• 分子量: 467.608
• InChiKey: UNHDWNYKAPCAPR-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  34.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  96.53
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Boc-Leu-Phe-NHBn 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以97%的产率得到
  参考文献：
  名称：

  Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction

  摘要：

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.

  DOI：

  10.1039/p19960002479
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 生成 Boc-Leu-Phe-NHBn
  参考文献：
  名称：

  Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction

  摘要：

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.

  DOI：

  10.1039/p19960002479

文献信息

• Imidazo[1,2- a ]pyridine-based peptidomimetics as inhibitors of Akt
  作者：Young B. Kim、Chang Won Kang、Sujeewa Ranatunga、Hua Yang、Said M. Sebti、Juan R. Del Valle

  DOI：10.1016/j.bmcl.2014.08.040

  日期：2014.10

  We report the design, synthesis, and biological evaluation of imidazopyridine-based peptidomimetics based on the substrate consensus sequence of Akt, an AGC family serine/threonine kinase hyperactivated in over 50% of human tumors. Our ligand-based approach led to the identification of novel substrate mimetic inhibitors of Akt1 featuring an unnatural extended dipeptide surrogate. Compound 11 inhibits Akt isoforms in the sub-micromolar range and exhibits improved proteolytic stability relative to a parent pentapeptide.