(R)-2-((r)-2-氨基-3-苯基丙酰胺)-3-苯基丙酸 | 58607-69-5

• 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
• 中文名称: (R)-2-((r)-2-氨基-3-苯基丙酰胺)-3-苯基丙酸
• 英文名称: D-phenylalaninyl-D-phenylalanine
• 英文别名: D,D-diphenylalanine；D-Phe-D-Phe；(D-F)2；H–DPheDPhe–OH；(D-Phe)-(D-Phe)；D-F-D-F；(2R)-2-[[(2R)-2-azaniumyl-3-phenylpropanoyl]amino]-3-phenylpropanoate
• CAS: 58607-69-5
• 化学式: C₁₈H₂₀N₂O₃
• 分子量: 312.368
• InChiKey: GKZIWHRNKRBEOH-HZPDHXFCSA-N

物化性质

• 熔点：
  130-131 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  582.8±50.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: H-D-Phe-D-Phe-OH
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: H-D-Phe-D-Phe-OH
CAS number: 58607-69-5

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C18H20N2O3
Molecular weight: 312.4

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (R)-2-((r)-2-氨基-3-苯基丙酰胺)-3-苯基丙酸 在 碳酸氢钠 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 (3S,7S,25R,28R)-tri-tert-butyl-33-azido-25,28-dibenzyl-12-(4-chlorobenzyl)-5,13,20,23,26,29-hexaoxo-4,6,12,19,24,27,30-heptaazatritriacontane-1,3,7-tricarboxylate
  参考文献：
  名称：

  基于它们的芳香族残基和荧光缀合物的PSMA配体的合成及生物学评价

  摘要：

  前列腺特异性膜抗原（PSMA），也称为谷氨酸羧肽酶II（GCPII），由于其在前列腺癌细胞中的过表达而成为抗肿瘤药物和诊断剂特异性递送的合适靶标。在当前的工作中，我们描述了新型的低分子PSMA配体和缀合物与荧光染料FAM-5，SulfoCy5和SulfoCy7的设计，合成和生物学评估。合成的PSMA配体对PSMA活性的体外评估表明，将芳香族氨基酸添加到接头结构中会导致抑制作用的显着增加。最有效的配体与FAM-5以及SulfoCy5的结合物在体外表现出对表达PSMA的肿瘤细胞的高亲和力。体内具有新型PSMA配体的PSMA-SulfoCy5和PSMA-SulfoCy7偶联物在Balb / c裸鼠的22Rv1异种移植物中的生物分布显示了表达PSMA的肿瘤的良好可视化。而且，缀合物PSMA-SulfoCy7证明不存在任何高达87.9 mg / kg的明确毒性。

  DOI：

  10.1021/acs.jmedchem.0c01935
• 作为产物：
  描述：

  DL-苯丙氨酸苄酯 在 Streptomyces spp. 82F₂ D-aminopeptidase 作用下， 以 二甲基亚砜 为溶剂， 生成 (R)-2-((r)-2-氨基-3-苯基丙酰胺)-3-苯基丙酸
  参考文献：
  名称：

  Aminolytic reaction catalyzed by d-stereospecific amidohydrolases from Streptomyces spp

  摘要：

  From investigation of 2000 soil isolates, we identified two serine-type amidohydrolases that can hydrolyze D-aminoacyl derivatives from the culture supernatant of Streptomyces species 82F2 and 83D12. The enzymes, redesignated as 82F2-DAP and 83D12-DAP, were purified for homogeneity and characterized. Each enzyme had molecular mass of approximately 40 kDa, and each showed moderate stability with respect to temperature and pH. Among hydrolytic activities toward D-aminoacyl-pNAs, the enzymes showed strict specificity toward D-Phe-pNA, but showed broad specificity toward D-aminoacyl esters. The specific activity for D-Phe-pNA hydrolysis of 82F2-DAP was ten-fold higher than that of 83D12-DAP. As a second function, each enzyme showed peptide bond formation activity by its function of aminolysis reaction. Based on results of D-Phe D-Phe synthesis under various conditions, we propose a reaction mechanism for D-Phe D-Phe production. Furthermore, the enzymes exhibited peptide elongation activity, producing oligo homopeptide in a one-pot reaction. We cloned the genes encoding each enzyme, which revealed that the primary structure of each enzyme showed 30-60% identity with those of peptidases belonging to the clan SE, S12 peptidase family categorized as serine peptidase with D-stereospecificity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biochi.2011.04.020

文献信息

• Search for Fibrous Aggregates Potentially Useful in Regenerative Medicine Formed under Physiological Conditions by Self-Assembling Short Peptides Containing Two Identical Aromatic Amino Acid Residues
  作者：Justyna Fraczyk、Wojciech Lipinski、Agata Chaberska、Joanna Wasko、Kamil Rozniakowski、Zbigniew Kaminski、Maciej Bogun、Zbigniew Draczynski、Elzbieta Menaszek、Ewa Stodolak-Zych、Marta Kaminska、Beata Kolesinska

  DOI：10.3390/molecules23030568

  日期：——

  peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established

  本研究调查了短肽自组织的倾向以及聚集体对细胞培养的影响。二肽衍生自相同芳香族氨基酸的两种对映异构体，而三肽由两种相同芳香族氨基酸制备，在 C 端、N 端或中心位置具有一个半胱氨酸或甲硫氨酸残基。使用刚果红和硫黄素 T 测定以及通过使用正常和偏振光的显微镜检查确定生理条件下纤维结构的形成或不存在。评估了 30 天后在缓冲盐水溶液中聚集体的体外稳定性。根据肽对内皮细胞系 EA 的细胞毒性选择具有用于再生医学的潜力的材料。hy 926 和薄膜表面的润湿性，以及使用扫描电子显微镜。H-dPhedPhe-OH、H-dCysdPhedPhe-OH、H-CysTyrTyr-OH、H-dPhedPhedCys-OH、H-TyrTyrMet-OH 和 H-TyrMetTyr-OH 满足标准。我们的初步结果表明 L919 成纤维细胞的形态和细胞活力不依赖于自组织肽的立体化学。
• The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels
  作者：Jiayang Li、Yi Kuang、Junfeng Shi、Yuan Gao、Jie Zhou、Bing Xu

  DOI：10.3762/bjoc.9.104

  日期：——

  Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The covalent linkage of Phe–Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1), the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc) of 0.2 wt % at pH 7.0. Hydrogelator 1a, also acting as a general motif, enables enzymatic hydrogelation in which the precursor turns into a hydrogelator upon hydrolysis catalyzed by a phosphatase at physiological conditions. The conjugates of Phe–Phe with other NSAIDs, such as (R)-flurbiprofen (2), racemic flurbiprofen (3), and racemic ibuprofen (4), are able to form molecular hydrogels, except in the case of aspirin (5). After the conjugation with the small peptides, NSAIDs exhibit improved selectivity to their targets. In addition, the peptides made of D-amino acids help preserve the activities of NSAIDs. Besides demonstrating that common NSAIDs are excellent candidates to promote aromatic–aromatic interaction in water to form hydrogels, this work contributes to the development of functional molecules that have dual or multiple roles and ultimately may lead to new molecular hydrogels of therapeutic agents for topical use.

  在这里，我们报告了由非甾体抗炎药（NSAID）和小肽组成的超分子水凝胶剂。Phe–Phe和NSAIDs的共价连接产生了在水溶液中自组装形成分子纳米纤维作为水凝胶基质的偶联物。当NSAID是萘普生（1）时，所得的水凝胶剂1a在pH 7.0的临界浓度（cgc）为0.2 wt%时形成水凝胶。水凝胶剂1a，也作为一种通用结构，能够进行酶促水凝胶化，即前体在生理条件下经磷酸酶催化的水解转变为水凝胶剂。Phe–Phe与其他NSAIDs，如（R）-氟比洛芬（2）、消旋氟比洛芬（3）和消旋布洛芬（4）的偶联物能够形成分子水凝胶，但在阿司匹林（5）的情况下则不能。与小肽偶联后，NSAIDs对其靶标的选择性得到提高。此外，由D-氨基酸组成的小肽有助于保持NSAIDs的活性。除了证明常见的NSAIDs是促进水溶液中芳香族-芳香族相互作用以形成水凝胶的优秀候选者外，这项工作还促进了具有双重或多重功能的功能分子的发展，并最终可能导致用于外用治疗剂的新型分子水凝胶的产生。

• A novel aggregation-induced emission enhancement triggered by the assembly of a chiral gelator: from non-emissive nanofibers to emissive micro-loops
  作者：Wenrui Chen、Guangyan Qing、Taolei Sun

  DOI：10.1039/c6cc08808b

  日期：——

  In this study, a novel aggregation-induced emission (AIE) enhancement triggered by the self-assembly of chiral gelator is described. Tuning of molecular chirality in situ triggers different assemblies of superstructures exhibiting...

  在这项研究中，描述了由手性胶凝剂的自组装触发的新型聚集诱导发射（AIE）增强。分子手性的原位调节可触发显示出...
• Peptide bond formation by aminolysin-A catalysis: A simple approach to enzymatic synthesis of diverse short oligopeptides and biologically active puromycins
  作者：Hirokazu Usuki、Yukihiro Yamamoto、Jiro Arima、Masaki Iwabuchi、Shozo Miyoshi、Teruhiko Nitoda、Tadashi Hatanaka

  DOI：10.1039/c0ob00403k

  日期：——

  peptide bonds to give linear homo-oligopeptides, hetero-dipeptides, and cyclic dipeptides using cost-effective substrates in a one-pot reaction. Aminolysin-A can recognize several C-terminal-modified amino acids, including the L- and D-forms, as acyl donors as well as free amines, including amino acids and puromycin aminonucleoside, as acyl acceptors. The absence of amino acid esters prevents the formation

  新S9系列的氨肽酶从嗜热放线菌衍生Acidothermus了解纤维素被催化丝氨酸的定点突变克隆和工程化到transaminopeptidase 491到半胱氨酸。经过工程改造的生物催化剂，称为氨基溶素A，可以在一锅反应中使用经济高效的底物来催化肽键的形成，从而生成线性同型寡肽，杂二肽和环状二肽。氨基溶素A可以识别多个C末端修饰的氨基酸（包括L-和D-形式）作为酰基供体，以及游离胺（包括氨基酸和嘌呤霉素氨基核苷）作为酰基受体。氨基酸酯的缺乏阻止了肽的形成。因此，反应机理涉及氨解而不是水解的逆反应。氨基溶素系统将是通过简单方法制备结构多样的肽模拟物的有益工具。
• Chiral adaptive recognition with sequence specificity of aromatic dipeptides in aqueous solution by an achiral cage
  作者：Lin Cheng、Ping Tian、Honghong Duan、Qingfang Li、Xiaowen Song、Anyang Li、Liping Cao

  DOI：10.1039/d2sc05854e

  日期：——

  dipeptides to form 1 : 2 host–guest complexes with high binding affinity (>1010 M−2), especially up to ∼1014 M−2 for TrpTrp. Given the dynamic rotational conformation of TPE units, achiral 1 can exhibit chiral adaptive responses with mirror-symmetrical circular dichroism (CD) and circularly polarized luminescence (CPL) spectra to enantiomeric dipeptides via supramolecular chirality transfer in the host–guest

  通过合成化合物或系统对肽和蛋白质进行序列特异性识别仍然是生物相容性介质中的一个巨大挑战。在这里，我们使用基于四苯乙烯的非手性八阳离子笼 ( 1 ) 作为分子受体和手性光学传感器，报告了在纯水溶液中具有芳香族二肽序列特异性的手性自适应识别 (CAR) 。1可以选择性地结合和二聚化芳香族二肽，形成 1 : 2 主客体复合物，具有高结合亲和力 (>10 10 M -2 )，尤其是高达∼10 14 M -2的 TrpTrp。鉴于 TPE 单元的动态旋转构象，非手性1可以通过主客体复合物中的超分子手性转移对对映体二肽表现出镜像对称圆二色性 (CD) 和圆偏振发光 (CPL) 光谱的手性适应性响应。此外，这种序列特异性为1的 CAR可用于分子识别含有 TrpTrp 或 PhePhe 的四肽、多肽（例如，淀粉样蛋白 β-肽1-20和生长抑素）和具有特征性 CD 的蛋白质（例如，人胰岛素）回应。