BOC-Ala-Phe-NH2 | 27220-69-5

• 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-Ala-Phe-NH2
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]carbamate
• CAS: 27220-69-5
• 化学式: C₁₇H₂₅N₃O₄
• 分子量: 335.403
• InChiKey: XYLBJSWNDGRKJP-AAEUAGOBSA-N

物化性质

• 熔点：
  154-155 °C
• 沸点：
  601.2±55.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  BOC-Ala-Phe-NH2 在 三氟乙酸 作用下， 反应 1.0h， 生成 L-苯丙氨酸酰胺,L-丙氨酰-
  参考文献：
  名称：

  Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists

  摘要：

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.

  DOI：

  10.1021/jm000937a
• 作为产物：
  描述：

  L-苯丙氨酰胺盐酸盐 、 Boc-L-丙氨酸 N-丁二酰亚胺酯 在 碳酸氢钠 作用下， 以 乙二醇二甲醚 为溶剂， 生成 BOC-Ala-Phe-NH2
  参考文献：
  名称：

  Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists

  摘要：

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.

  DOI：

  10.1021/jm000937a

文献信息

• Facile Amide Bond Formation From Esters of Amino Acids and Peptides Catalyzed by Alkaline Protease in Anhydrous<i>tert</i>-Butyl Alcohol Using Ammonium Chloride/Triethylamine as a Source of Nucleophilic Ammonia
  作者：Shui-Tein Chen、Ming-Kuei Jang、Kung-Tsung Wang

  DOI：10.1055/s-1993-25955

  日期：——

  An industrial alkaline protease "Alcalase", stable and active in tert-butyl alcohol, was used to catalyze the synthesis of N-protected amino acids or peptide amides in anhydrous tert-butyl alcohol using ammonium chloride/triethylamine as source of nucleophilic ammonia

  一种工业碱性蛋白酶 "Alcalase"，其在叔丁醇中稳定且具有活性，被用于在无水叔丁醇中使用氯化铵/三乙胺作为亲核氨源，催化合成 N-保护氨基酸或肽酰胺。
• Polypeptides. Part XII. The preparation of 2-pyridyl esters and their use in peptide synthesis
  作者：A. S. Dutta、J. S. Morley

  DOI：10.1039/j39710002896

  日期：——

  amino-acid derivatives, and hydroxy-compounds) than the corresponding p-nitrophenyl esters. Evidence is presented that they are likely to be particularly useful in solid-phase peptide synthesis, and in the synthesis of O-peptides and depsipeptides.

  2-吡啶基的酯ñ -酰基氨基羧酸可从羧酸，2-羟基吡啶，并准备NN（仅“在吡啶-dicyclohexylcarbodi酰亚胺ñ在乙腈或二氯甲烷中形成-acylureas）。所述Ñ -t丁氧基-羰基-氨基甲酸2-吡啶基酯是大多结晶的，稳定的，并且在非极性溶剂相当对亲核试剂（胺，氨基-酯和酰胺更具反应性的，受阻氨基酸衍生物，和羟基化合物）比相应的对硝基苯酯。证据表明，它们可能在固相肽合成以及O肽和depsipeptide的合成中特别有用。
• Mechanoenzymatic peptide and amide bond formation
  作者：José G. Hernández、Karen J. Ardila-Fierro、Deborah Crawford、Stuart L. James、Carsten Bolm

  DOI：10.1039/c7gc00615b

  日期：——

  Mechanochemical chemoenzymatic peptide and amide bond formation catalysed by papain was studied by ball milling. Despite the high-energy mixing experienced inside the ball mill, the biocatalyst proved stable and highly efficient to catalyse the formation of α,α- and α,β-dipeptides. This strategy was further extended to the enzymatic acylation of amines by milling, and to the mechanosynthesis of a derivative

  通过球磨研究了木瓜蛋白酶催化的机械化学化学酶促肽和酰胺键的形成。尽管在球磨机内部经历了高能混合，但是生物催化剂被证明是稳定且高效的，以催化α，α-和α，β-二肽的形成。该策略进一步扩展到通过研磨将胺酶促酰化，并扩展到有价值的二肽L-丙氨酰基-L-谷氨酰胺衍生物的机械合成。
• Structural studies of [2′,6′-dimethyl-l-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond
  作者：Yoshio Okada、Yoshio Fujita、Takashi Motoyama、Yuko Tsuda、Toshio Yokoi、Tingyou Li、Yusuke Sasaki、Akihiro Ambo、Yunden Jinsmaa、Sharon D. Bryant、Lawrence H. Lazarus

  DOI：10.1016/s0968-0896(03)00068-3

  日期：2003.5

  Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i)mu = 0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta = 28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC50 = 0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu 13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2) = 7.05). H-1 NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists
  作者：Caroline M. R. Low、James W. Black、Howard B. Broughton、Ildiko M. Buck、Jonathan M. R. Davies、David J. Dunstone、Robert A. D. Hull、S. Barret Kalindjian、Iain M. McDonald、Michael J. Pether、Nigel P. Shankley、Katherine I. M. Steel

  DOI：10.1021/jm000937a

  日期：2000.9.1

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.