Boc-Leu-βGly-OH | 129505-34-6

• 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: Boc-Leu-βGly-OH
• 英文别名: Boc-Leu-βAla-OH；Boc-L-Leu-β-Ala；t-Butyloxycarbonyl-L-Leucyl-beta-Alanine；3-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]propanoic acid
• CAS: 129505-34-6
• 化学式: C₁₄H₂₆N₂O₅
• 分子量: 302.371
• InChiKey: XUKXAWDUICMCKG-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Leu-βGly-OH 、 L-valyl-L-valine methyl ester 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 Boc-Leu-βGly-Val-Val-OMe
  参考文献：
  名称：

  包含α-和ω-氨基酸的杂合肽发夹：十肽在3和8位具有未取代的β-，γ-和δ残基的构象分析

  摘要：

  通过使用四种合成十肽Boc-Leu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val研究了将未取代的ω-氨基酸插入模型β-发夹肽的链节中的作用-OMe：肽1（Xxx = Gly），肽2（Xxx = betaGly = betahGly =同甘氨酸，β-甘氨酸），肽3（Xxx = gammaAbu =γ-氨基丁酸），肽4（Xxx = deltaAva =δ-氨基戊酸酸）。1 H NMR研究（500 MHz，甲醇）显示了几个关键的交叉链NOE，为肽2-4中的β-发夹构象提供了证据。在肽3中，NMR结果支持成核转角的形成，但是，没有检测到交叉链配体的证据。肽3的单晶X射线衍射研究揭示了晶体不对称单元中两个分子的β-发夹构象，通过四个交叉链氢键稳定，其中gammaAbu残基容纳在链内。两个分子（A，B）中的D-Pro-Gly区段都采用II型β-转角构象。肽3的圆二色性光谱的特征是在229

  DOI：

  10.1002/chem.200500742
• 作为产物：
  描述：

  Boc-Leu-βAla-OEt 在 lithium hydroxide monohydrate 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以100%的产率得到Boc-Leu-βGly-OH
  参考文献：
  名称：

  微调肽硫酯环化和外消旋化之间的平衡

  摘要：

  对含有 - 氨基酸和 - 丙氨酸的七元双内酰胺的闭环是有问题的。这种困难的内酰胺化伴随着副反应，例如水解、低聚和外消旋。通过从线性肽 4-甲氧基苯硫酚酯开始，与磷酸盐缓冲液 (pH 6.8) 结合稀释至 1 mM，可以在很大程度上抑制分子间反应和外消旋化。在 C 端具有手性残基的硫酯以高达 60% 的产率和高达 99% 的对映体过量得到双内酰胺。对映体纯双内酰胺仅从 C 端带有丙氨酸的反向序列中获得。

  DOI：

  10.1002/ejoc.201501366

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。
• Novel C-terminal gastrin antagonists
  申请人：——

  公开号：US04997950A1

  公开（公告）日：1991-03-05

  A series of derivatives of the biologically active C-terminus of gastrin was synthesized to study the structural activity of the molecule and also to determine the smallest and highest affinity inhibitor of gastrin. Earlier work speculated that a peptide resistant to dipeptidase contained in a receptor would be an effective gastrin antagonist. Methods: Five dogs with both chronic gastric fistulae and Heidenhein pouches were used. After an 18 hour fast, gastric juice was collected both from the gastric fistula and pouch over 200 minutes at 10 minute intervals. MMC (Migrating Motor Complex) was monitored by a small balloon in the gastric antrum. Collections were initiated at the beginning of phase I of the MMC and were obtained under 3 conditions: Control, pentagastrin infusion (0.5 .mu.g/Kg/h, i.v.) and pentagastrin+peptide infusion (Indole propionic acid [IPA]- Leu-Asp-Phenethyl amine [PEA], Boc-Trp-Leu-.beta.Ala, IPA-Leu-.beta.Ala, or Boc-Trp-Leu-Asp-methyl meta Aminobenzoic acid mABAOMe] at 20 pmol/kg/h for 70 min.). Pentagastrin infusion was started immediately before the next peak of the MMC. Peptides were infused 60 minutes after starting pentagastrin infusion. Results: All four peptides inhibited the stimulated acid secretion causing it to approach the control level. ______________________________________ Inhibition of the stimulated acid secretion (.DELTA. meq/kg) Heidenhein Gastric Fistula Pouch ______________________________________ IPA--Leu--Asp--PEA .dwnarw.303 .+-. 120* .dwnarw.18 .+-. 11* Boc--Trp--Leu-.beta.Ala .dwnarw.618 .+-. 168** .dwnarw.35 .+-. 8** IPA--Leu-.beta.Ala .dwnarw.562 .+-. 249* .dwnarw.34 .+-. 12* Boc--Trp--Leu--Asp- .dwnarw.446 .+-. 172** .dwnarw.40 .+-. 16** mABAOMe ______________________________________ (*p < 0.05 **p < 0.01, mean .+-. s.e.) PAL It is concluded that even small di-and tripeptide derivatives of the gastrin C-terminal fragment with varied resistance to hydrolysis can exhibit antagonist activity to pentagastrin stimulated gastric acid secretion.

  为了研究胃泌素分子的结构活性并确定最小和最高亲和力的胃泌素抑制剂，合成了一系列具有生物活性的胃泌素C-末端衍生物。先前的研究推测，对受体中存在的二肽酶抵抗性肽肽可能是有效的胃泌素拮抗剂。方法：使用了五只同时患有慢性胃瘘和海登海因囊的狗。在18小时禁食后，以10分钟间隔在200分钟内从胃瘘和囊中收集胃液。通过胃窦中的小气球监测MMC（迁移性运动复合物）。收集是在MMC的第一阶段开始时启动的，并在三种情况下进行：对照组、五肽胃泌素注射（0.5μg / Kg / h，i.v.）和五肽胃泌素+肽注射（吲哚丙酸[IPA]-亮-天冬氨酸-苯乙胺[PEA]，Boc-色氨酸-亮-β-丙氨酸，IPA-亮-β-丙氨酸或Boc-色氨酸-亮-天冬氨酸-甲基间氨基苯甲酸mABAOMe]，每小时20 pmol / kg，持续70分钟）。五肽胃泌素注射是在MMC的下一个峰值前立即开始的。肽注射是在开始五肽胃泌素注射后60分钟进行的。结果：所有四个肽都抑制了刺激酸分泌，使其接近对照水平。______________________________________刺激酸分泌的抑制（Δmeq / kg）海登海因胃瘘囊________________________________________吲哚丙酸-亮-天冬氨酸-苯乙胺.dwnarw.303 .+-. 120 * .dwnarw.18 .+-. 11 *Boc-色氨酸-亮-β-丙氨酸.dwnarw.618 .+-. 168 ** .dwnarw.35 .+-. 8 **IPA-亮-β-丙氨酸.dwnarw.562 .+-. 249 * .dwnarw.34 .+-. 12 *Boc-色氨酸-亮-天冬氨酸-甲基间氨基苯甲酸.dwnarw.446 .+-. 172 ** .dwnarw.40 .+-. 16 **mABAOMe______________________________________（*p＜0.05 **p＜0.01，平均值.+-. s.e.）PAL得出结论，即即使是胃泌素C末端片段的小二肽和三肽衍生物，具有不同的水解抵抗性，也可以表现出对五肽胃泌素刺激的胃酸分泌的拮抗作用。
• Leucinostatin Y: A Peptaibiotic Produced by the Entomoparasitic Fungus <i>Purpureocillium lilacinum</i> 40-H-28
  作者：Isao Momose、Takefumi Onodera、Hiroyasu Doi、Hayamitsu Adachi、Masatomi Iijima、Yohko Yamazaki、Ryuichi Sawa、Yumiko Kubota、Masayuki Igarashi、Manabu Kawada

  DOI：10.1021/acs.jnatprod.8b00839

  日期：2019.5.24

  Leucinostatin Y, a new peptaibiotic, was isolated from the culture broth of the entomoparasitic fungus Purpureocillium lilacinum 40-H-28. The planar structure was elucidated by detailed analysis of its NMR and MS/MS data. The absolute configurations of the amino acids were partially determined by an advanced Marfey's method. The biological activities of leucinostatin Y were assessed using human pancreatic cancer cells, revealing the importance of the C-terminus of leucinostatins for preferential cytotoxicity to cancer cells under glucose-deprived conditions and inhibition of mitochondrial function.
• YASUI, AKIHIRO;DOUGLAS, ALASTAIR J.;WALKER, BRIAN;MAGEE, DONAL F.;MURPHY,+, INT. J. PEPTIDE AND PROTEIN RES., 35,(1990) N, C. 301-305
  作者：YASUI, AKIHIRO、DOUGLAS, ALASTAIR J.、WALKER, BRIAN、MAGEE, DONAL F.、MURPHY,+

  DOI：——

  日期：——
• US4997950A
  申请人：——

  公开号：US4997950A

  公开（公告）日：1991-03-05