Fmoc-alpha-甲基-l-苯丙氨酸 | 135944-05-7

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: Fmoc-alpha-甲基-l-苯丙氨酸
• 中文别名: 芴甲氧羰基-α-甲基-苯丙氨酸；FMOC-Α-甲基-L-苯丙氨酸；FMOC-ALPHA-甲基-L-苯丙氨酸
• 英文名称: Fmoc-(α-Me)-Phe-OH
• 英文别名: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-2-methyl-3-phenylpropanoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methyl-3-phenylpropanoic acid
• CAS: 135944-05-7
• 化学式: C₂₅H₂₃NO₄
• 分子量: 401.462
• InChiKey: KLBKBAAOPOXFSK-VWLOTQADSA-N

物化性质

• 熔点：
  72-75°C
• 沸点：
  621.2±50.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMF（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• TSCA：
  No
• 危险等级：
  IRRITANT
• 海关编码：
  2924299090
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-alpha-methyl-L-phenylalanine
Synonyms: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-2-methyl-3-phenylpropanoic acid

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

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Section 3. Composition/information on ingredients.
Ingredient name: Fmoc-alpha-methyl-L-phenylalanine
CAS number: 135944-05-7

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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.

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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.

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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.

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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:

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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.

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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: C25H23NO4
Molecular weight: 401.5

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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.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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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.

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

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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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  Fmoc-alpha-甲基-l-苯丙氨酸 在 三乙基硅烷 、 camphor-10-sulfonic acid 、 四氯化钛 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 (2S)-2-[9H-fluorene-9-ylmethoxycarbonyl(methyl)amino]-2-methyl-3-phenylpropanoic acid
  参考文献：
  名称：

  JP6880352

  摘要：

  公开号：
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 2-甲基-L-苯丙氨酸一水物 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以2.22 g的产率得到Fmoc-alpha-甲基-l-苯丙氨酸
  参考文献：
  名称：

  凝血酶受体激活肽（TRAP）：通过结构活性，光谱学和计算研究来研究生物活性构象。

  摘要：

  凝血酶受体（PAR-1）是一种不常见的跨膜G蛋白偶联受体，它通过丝氨酸蛋白酶裂解其胞外N端而被激活，从而暴露出激动剂肽配体，并与受体本身拴在一起。包含激动剂基序的合成肽，例如人PAR-1的SFLLRN，能够引起完全的受体活化。我们通过系统引入某些构象扰动（包括α-甲基，酯psi（COO）和还原酰胺psi（CH2N）扫描），将凝血酶受体激活肽（TRAPs）的可能的生物活性构象探究到最低限度激动剂序列（SFLLR），以探测骨架构象和酰胺NH氢键的重要性。我们进行了代表性五肽的广泛构象搜索，以推导假定的生物活性结构家族。此外，我们采用1 H NMR和圆二色性（CD）通过实验表征某些五肽类似物的构象。我们的五肽类似物激活的血小板聚集提供了PAR-1激动剂活性的结构-功能相关性。PAR-1受体结合数据辅助了这种相关性，PAR-1受体结合数据确定了肽配体对凝血酶受体的亲和力，而与源自受体激活（即纯分子

  DOI：

  10.1016/s0968-0896(99)00180-7

文献信息

• Selection of DNA‐Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery
  作者：Yuqing Deng、Jianzhao Peng、Feng Xiong、Yinan Song、Yu Zhou、Jianfu Zhang、Fong Sang Lam、Chao Xie、Wenyin Shen、Yiran Huang、Ling Meng、Xiaoyu Li

  DOI：10.1002/anie.202005070

  日期：2020.8.24

  that can identify full ligand structures from large‐scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. We demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4)

  动态组合库（DCL）是生物医学研究中配体发现的强大工具。但是，DCL的低多样性阻碍了它们的应用。最近，DCL中已经采用了DNA编码的概念来创建DNA编码的动态库（DEDL）。但是，当前所有的DEDL都仅限于片段识别，并且在选择后需要一个具有挑战性的片段链接过程。我们报告了一种锚定的DEDL方法，该方法可以从大规模DEDL中识别出完整的配体结构。这种方法还能够将无偏文库转换为针对特定蛋白质类别的集中文库。我们通过选择针对五种蛋白质的DEDLs证明了这种方法，并为所有靶标确定了新型抑制剂。值得注意的是 从针对重要的抗癌药物靶标bromodomain 4（BRD4）的选择中鉴定出了几种选择性的BD1 / BD2抑制剂。这项工作可以为抑制剂发现提供广泛适用的方法。
• Antibody peptide conjugates that have agonist activity at both the glucagon and glucagon-like peptide 1 receptors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10800826B2

  公开（公告）日：2020-10-13

  Described are antibody peptide conjugates (APCs) comprising an antibody conjugated to a peptide analog of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have agonist activity at the glucagon (GCG) receptor and the glucagon-like peptide 1 (GLP-1) receptor and the use of such APCs for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

  所述抗体多肽共轭物（APCs）包括与胰高血糖素多肽类似物共轭的抗体、经改良后可抗二肽基肽酶 IV（DPP-IV）的裂解和失活，并可延长肽类似物的体内半衰期，同时使肽类似物在胰高血糖素（GCG）受体和胰高血糖素样肽 1（GLP-1）受体上具有激动剂活性、非酒精性脂肪肝（NAFLD）、非酒精性脂肪性肝炎（NASH）和肥胖症等代谢性疾病。
• Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity
  作者：Claudio Mapelli、Sesha I. Natarajan、Jean-Philippe Meyer、Margarita M. Bastos、Michael S. Bernatowicz、Ving G. Lee、Jelka Pluscec、Douglas J. Riexinger、Ellen S. Sieber-McMaster、Keith L. Constantine、Constance A. Smith-Monroy、Rajasree Golla、Zhengping Ma、Daniel A. Longhi、Dan Shi、Li Xin、Joseph R. Taylor、Barry Koplowitz、Cecilia L. Chi、Ashish Khanna、Gordon W. Robinson、Ramakrishna Seethala、Ildiko A. Antal-Zimanyi、Robert H. Stoffel、Songping Han、Jean M. Whaley、Christine S. Huang、John Krupinski、William R. Ewing

  DOI：10.1021/jm900752a

  日期：2009.12.10

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.
• C-Terminal Modifications of Apelin-13 Significantly Change Ligand Binding, Receptor Signaling, and Hypotensive Action
  作者：Alexandre Murza、Élie Besserer-Offroy、Jérôme Côté、Patrick Bérubé、Jean-Michel Longpré、Robert Dumaine、Olivier Lesur、Mannix Auger-Messier、Richard Leduc、Philippe Sarret、Éric Marsault

  DOI：10.1021/jm501916k

  日期：2015.3.12

  Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family. This system plays an important role in the regulation of blood pressure and cardiovascular functions. To better understand the role of its C-terminal Phe13 residue on ligand binding, receptor signaling, and hypotension, we report a series of modified analogues in which Phe13 was substituted by unnatural amino acids. These modifications delivered new compounds exhibiting higher affinity and potency to inhibit cAMP accumulation compared to apelin-13. In particular, analogues Bpa(13) or (alpha-Me)Phe(13) were 30-fold more potent to inhibit cAMP accumulation than apelin-13. Tyr(OBn)(13) substitution led to a 60-fold improvement in binding affinity and induced stronger and more sustained drop in blood pressure compared to apelin-13. Our study identified new potent analogues of apelin-13, which represent valuable probes to better understand its structurefunction relationship.
• Constrained H-Phe-Phe-NH₂ Analogues with High Affinity to the Substance P 1–7 Binding Site and with Improved Metabolic Stability and Cell Permeability
  作者：Rebecca Fransson、Christian Sköld、Jadel M. Kratz、Richard Svensson、Per Artursson、Fred Nyberg、Mathias Hallberg、Anja Sandström

  DOI：10.1021/jm400209h

  日期：2013.6.27

  We recently reported the discovery, of H-Phe-Phe-NH2 as a small and high affinity ligand for the substance P 1-7 (SP1-7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) specific binding site and its intriguing ability to reduce neuropathic pain. With the overall aim to develop stable and orally bioavailable SP1-7 mimetics, the dipeptide was chosen as a lead compound. Herein the structure activity relationship (SAR) of a set of modified H-Phe-Phe-NH2 analogues is presented together with their potential active uptake by PEPT1 transporter, intestinal permeability, and metabolic stability. Local constraints via peptide backbone methylation or preparation of cyclized analogues based on pyrrolidine were evaluated and were shown to significantly improve the in vitro pharmacokinetic properties. The SAR was rationalized by deriving a plausible binding pose for the high affinity ligands. Rigidification using a 3-phenylpyrrolidine moiety in the C-terminal of H-Phe-Phe-NH2 resulted in high affinity and improved intrinsic clearance and intestinal epithelial permeability.