Boc-Tyr-D-Ala-Phe-OH | 94849-38-4

• 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-Tyr-D-Ala-Phe-OH
• 英文别名: Boc-L-Tyr-D-Ala-L-Phe-OH；(2S)-2-[[(2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoyl]amino]-3-phenylpropanoic acid
• CAS: 94849-38-4
• 化学式: C₂₆H₃₃N₃O₇
• 分子量: 499.564
• InChiKey: YESXFTWICMOFDR-CZAAIQMYSA-N

物化性质

• 沸点：
  819.2±65.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  154
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc-Tyr-D-Ala-Phe-OH 在 N-甲基吗啉 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 Tyr-D-Ala-Phe-Val-Val-Asp-Gly-NH2
  参考文献：
  名称：

  Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity

  摘要：

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.

  DOI：

  10.1016/0223-5234(92)90113-f
• 作为产物：
  描述：

  L-苯丙氨酸 在 sodium hydroxide 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 Boc-Tyr-D-Ala-Phe-OH
  参考文献：
  名称：

  Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity

  摘要：

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.

  DOI：

  10.1016/0223-5234(92)90113-f

文献信息

• Kinetically Controlled Peptide Synthesis Mediated by Papain Using the Carbamoylmethyl Ester as an Acyl Donor
  作者：Toshifumi Miyazawa、Takao Horimoto、Kayoko Tanaka

  DOI：10.1007/s10989-014-9393-0

  日期：2014.9

  carbamoylmethyl (Cam) esters as acyl donors in the presence of a cysteine protease, papain, immobilized on Celite. Several segment condensations were also achieved generally in high yields without danger of racemization and formation of the secondary-hydrolysis product. Moreover, partial sequences of some bioactive peptides were prepared through segment condensations, and aimed-at peptides were obtained generally

  在固定于硅藻土的半胱氨酸蛋白酶木瓜蛋白酶存在下，通常以高收率合成一系列二肽，其中氨基甲酰基甲基（Cam）酯为酰基供体。通常也以高收率获得数个段的缩合，而没有消旋化和形成二次水解产物的危险。此外，一些生物活性肽的部分序列是通过片段缩合制备的，并且通常以高收率获得了针对性的肽，而没有羧基组分的C-末端残基的外消旋化。因此，在半胱氨酸介导的偶联中再次确定了Cam酯在动力学控制的肽合成中的优越性。 如先前报道的被丝氨酸蛋白酶催化的那些。
• Opioid Tripeptides Hybridized with <i>trans</i> -1-Cinnamylpiperazine as Proliferation Inhibitors of Pancreatic Cancer Cells in Two- and Three-Dimensional in vitro Models
  作者：Anna K. Laskowska、Anna K. Puszko、Piotr Sosnowski、Krzysztof Różycki、Piotr Kosson、Joanna Matalińska、Marek Durlik、Aleksandra Misicka

  DOI：10.1002/cmdc.201700453

  日期：2017.10.9

  synthetic peptidomimetics containing an opioid tripeptide fragment (Tyr‐R1‐R2‐; where R1 is d‐Ala or d‐Thr, and R2 is Phe or Trp) hybridized with trans‐1‐cinnamylpiperazine. These compounds are stable in plasma up to 96 h and exhibit low hemotoxicity and good inhibitory effects on cancer cell growth in two‐ and three‐dimensional in vitro models of pancreatic cancer.

  根据世界卫生组织，在未来几年中，胰腺癌患者的死亡率将增加。吉西他滨是治疗胰腺恶性肿瘤的首选方法，但是增加对该药物的耐药性会降低其整体疗效。目前，许多研究小组正在进行针对新陈代谢途径，生长因子抑制剂以及肿瘤基质或肿瘤干细胞的新疗法的研究。本文我们报告含有阿片样三肽片段的合成肽模拟物的生物活性性质（细胞毒性和溶血活性）（酪氨酸-R 1 -R 2 - ;其中R 1是ð -Ala或d -Thr，且R 2为Phe或Trp）与...杂交反式-1-肉桂基哌嗪。这些化合物在长达96小时的血浆中稳定，在胰腺癌的二维和三维体外模型中显示出较低的血液毒性和对癌细胞生长的良好抑制作用。
• Design and Synthesis of 1-Aminocycloalkane-1-carboxylic Acid-Substituted Deltorphin Analogues:  Unique δ and μ Opioid Activity in Modified Peptides
  作者：Angela Breveglieri、Remo Guerrini、Severo Salvadori、Clementina Bianchi、Sharon D. Bryant、Martti Attila、Lawrence H. Lazarus

  DOI：10.1021/jm950490j

  日期：1996.1.1

  Deltorphin analogues were substituted by a series of achiral C-alpha,C-alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carbaxylic acids, Ac(x)c, where (x) = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac(6)(c)2,- des-Phe(3)]deltorphin C hexapeptide. Receptor assays indicated that even though Ac(6)c(2) and Ac(6)c(3) exhibited a diminished K-i delta by ca. 20-fold (2.5-3.3 nM) relative to deltorphin C (K-i delta = 0.15 nM), selectivity was marginally elevated (K-i mu/K-i delta = 1250) or enhanced by about 70%, and both peptides fitted stringent iterative calculations for a two-site binding model (eta = 0.625 and 0.766, respectively, P < 0.0001). The disubstituted [Ac(6)c(2,3)]- or [Ac(6)c(2),des-Phe(3)]deltorphin analogues yielded peptides with decreased K-i delta, such that the latter peptide was essentially inactive. The presence of Ac(5)c or Ac(3)c in place of Phe(3) further diminished K-i delta (15.4 to 19.0 nM), yet delta selectivity only fell about one-half(K-i mu/K-i delta = 440 and 535, respectively), and only the former peptide fitted a two-site binding model (eta = 0.799). The replacement of Asp(4) by Ac(6)c, Ac5c, or Ac(3)c produced essentially nonselective analogues through the acquisition of high mu affinities (2.5, 0.58, and 0.27 nM, respectively) while maintaining high delta affinities (K-i delta = 0.045-0;054 nM) which were about 3 fold greater than that of deltorphin C. Using pharmacological assays in vitro (mouse vas deferens and guinea pig ileum), position 3-substituted analogues all indicated substantial losses in bioactivity, whereas substitution by 1-aminocycloalkanes at the fourth position retained high delta activity. In fact, the bioactivity of [Ac(3)c(4)]deltorphin C indicated a peptide with relatively weak delta selectivity, which was comparable to the observations with the receptor binding data. In summary, the data confirmed that (i) delta selectivity occurs in the absence of D-chirality at position 2, (ii) the aromaticity of Phe(3) is replaceable by an achiral residue with a hydrophobic ring-saturated side chain, and (iii) the acquisition of dual high-affinity analogues occurs through the elimination of the anionic function at position 4 and replacement by an amino acid with a hydrophobic side chain.
• Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity
  作者：LH Lazarus、S Salvadori、P Grieco、WE Wilson、R Tomatis

  DOI：10.1016/0223-5234(92)90113-f

  日期：1992.11

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.