Boc-Leu-Ala-Val-OH | 123253-88-3

• 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-Ala-Val-OH
• 英文别名: (2S)-3-methyl-2-[[(2S)-2-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]propanoyl]amino]butanoic acid
• CAS: 123253-88-3
• 化学式: C₁₉H₃₅N₃O₆
• 分子量: 401.503
• InChiKey: ZNLCNUGCEROBQD-IHRRRGAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-[2-((S)-2-Amino-4-methyl-pentanoylamino)-2-methyl-propionylamino]-3-methyl-butyric acid methyl ester 、 Boc-Leu-Ala-Val-OH 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 Boc-Leu-Ala-Val-Leu-Aib-Val-OMe
  参考文献：
  名称：

  Conformational variability in short acyclic peptides. Stabilization of multiple β-turn structures in organic solvents

  摘要：

  The conformational characteristics of three hexapeptides Boc-Leu-Xxx-Val-Leu-Aib-Val-OMe (Xxx = Ala 1, D-Ala 2, Gly 3; Aib = alpha-aminoisobutyryl) have been probed in CDCl3 solution by NMR methods using solvent perturbation of chemical shifts and radical broadening of NH resonances to delineate intramolecularly hydrogen bonded NH groups, Nuclear Overhauser effects (NOEs) provide additional information on preferred backbone conformations, The substituent at position 2 acts as a major conformational determinant, While a continuous 3(10) helical conformation is favoured for the peptide with Xxx = Ala, a multiple beta-turns conformation is supported by both NMR and CD data for the peptide with Xxx = D-Ala, In the peptide with Xxx = Gly CD and NMR data suggest that both 3(10) helical and multiple turns conformations are simultaneously populated, The results suggest that incorporation of D-amino acids and Aib residues into all L-sequences may prove useful in generating sequences containing multiple turns.

  DOI：

  10.1039/p29960002701
• 作为产物：
  描述：

  丙氨酰-纈氨酸甲酯 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 Boc-Leu-Ala-Val-OH
  参考文献：
  名称：

  Conformational variability in short acyclic peptides. Stabilization of multiple β-turn structures in organic solvents

  摘要：

  The conformational characteristics of three hexapeptides Boc-Leu-Xxx-Val-Leu-Aib-Val-OMe (Xxx = Ala 1, D-Ala 2, Gly 3; Aib = alpha-aminoisobutyryl) have been probed in CDCl3 solution by NMR methods using solvent perturbation of chemical shifts and radical broadening of NH resonances to delineate intramolecularly hydrogen bonded NH groups, Nuclear Overhauser effects (NOEs) provide additional information on preferred backbone conformations, The substituent at position 2 acts as a major conformational determinant, While a continuous 3(10) helical conformation is favoured for the peptide with Xxx = Ala, a multiple beta-turns conformation is supported by both NMR and CD data for the peptide with Xxx = D-Ala, In the peptide with Xxx = Gly CD and NMR data suggest that both 3(10) helical and multiple turns conformations are simultaneously populated, The results suggest that incorporation of D-amino acids and Aib residues into all L-sequences may prove useful in generating sequences containing multiple turns.

  DOI：

  10.1039/p29960002701

文献信息

• Synthesis of New Peptide Derivatives of Galanthamine Designed for Prevention and Treatment of Alzheimer’s Disease
  作者：Lyubomir Vezenkov、Lilia Ilieva、Dancho Danalev、Anastasia Bakalova、D. Vassilev、Nikolai Danchev、Irina Nikolova

  DOI：10.2174/0929866522666150701111642

  日期：2015.8.21

  New derivatives of galanthamine containing peptide fragments with β-secretase inhibitor activity were synthesized. In position 6 of the galanthamine new shortened analogues of β-secretase inhibitor OM 99-2 (Boc-Val-Asn-Leu-Ala-OH and Boc-Val-Asn-Leu-Ala-Val-OH) were included. The new derivatives of the galanthamine in position 11 including Boc and norgalanthamine in P3 or P4 positions, Val in P2’ position and benzylamin in P3’-position were also synthesized. All new peptides were investigated on mice for acute toxicity. The test compounds were administered to mice via intraperitoneal (i.p.) route. They have low toxicity (LD501000 mg/kg) after i.p. The compound 11-N-demethyl-11-N-N-[Boc-Asp(Asp-Leu-Ala-Val-NH-Bzl)]-Galanthamine was investigated by two way active avoidance method. The compound has good influence on the conditioned reflexes, which improved the processes of learning and memory. Inhibition activity of newly synthesized compounds was monitored against BuChE and IC50 values are determined. All compounds show activity in micromolar concentration. Compounds 5 and 6 have around 10 times higher activity than galanthamine. Compounds 4 and 9 also show good activity. All newly synthesized compounds show low acute toxicity.

  合成了含有β-分泌酶抑制剂活性肽片段的加兰他敏新衍生物。在加兰他敏的第6位，合成了β-分泌酶抑制剂OM 99-2的新缩短类似物（Boc-Val-Asn-Leu-Ala-OH和Boc-Val-Asn-Leu-Ala-Val-OH）；在第11位，合成了加兰他敏的新衍生物，包括P3或P4位的Boc和去甲加兰他敏、P2'位的Val和P3'位的苄胺。对所有新肽进行了小鼠急性毒性研究。小鼠通过腹腔注射（i.p.）的方式摄入试验化合物。采用双向主动回避法研究了 11-N-demethyl-11-N-N-[Boc-Asp(Asp-Leu-Ala-Val-NH-Bzl)]-Galanthamine 化合物。该化合物对条件反射具有良好的影响，可改善学习和记忆过程。对新合成化合物对 BuChE 的抑制活性进行了监测，并测定了 IC50 值。所有化合物在微摩尔浓度下均显示出活性，其中化合物 5 和 6 的活性约为加兰他敏的 10 倍。所有新合成的化合物都显示出较低的急性毒性。