N-[(9H-芴-9-基甲氧基)羰基]-N-甲基-N'-[(4-甲氧基-2,3,6-三甲苯基)磺酰基]-L-精氨酸 | 214750-72-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 精氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-[(9H-芴-9-基甲氧基)羰基]-N-甲基-N'-[(4-甲氧基-2,3,6-三甲苯基)磺酰基]-L-精氨酸
• 中文别名: N-[(9H-芴-9-基甲氧基)羰基]-N-甲基-N’-[(4-甲氧基-2,3,6-三甲苯基)磺酰基]-L-精氨酸
• 英文名称: Fmoc-N-Me-Arg(Mtr)-OH
• 英文别名: (2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]pentanoic acid
• CAS: 214750-72-8
• 化学式: C₃₂H₃₈N₄O₇S
• 分子量: 622.742
• InChiKey: LNVHMIGZISCVKC-MHZLTWQESA-N

物化性质

• 沸点：
  798.5±70.0 °C(Predicted)
• 密度：
  1.32

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  169
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• 危险等级：
  IRRITANT
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,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-n-me-arg(mtr)-oh
Synonyms:

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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-n-me-arg(mtr)-oh
CAS number: 214750-72-8

---

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.

---

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.
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: C32H38N4O7S
Molecular weight: 622.7

---

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, sulfur oxides.

---

Section 11. Toxicological information
No data.

---

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.

---

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：

  N-[(9H-芴-9-基甲氧基)羰基]-N-甲基-N'-[(4-甲氧基-2,3,6-三甲苯基)磺酰基]-L-精氨酸 、 Fmoc-L-缬氨酸 、 Fmoc-L-苯丙氨酸 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 N-芴甲氧羰基-L-组氨酸 在 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 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.28h， 以21%的产率得到K-(N-Me-R)-VHF-NH₂
  参考文献：
  名称：

  Short peptide pharmacophores developed from protein phosphatase-1 disrupting peptides (PDPs)

  摘要：

  DOI：

  10.1016/j.bmc.2022.116785

文献信息

• Development of a Metabolically Stable Neurotensin Receptor 2 (NTS2) Ligand
  作者：Cornelia Held、Manuel Plomer、Harald Hübner、Jasmin Meltretter、Monika Pischetsrieder、Peter Gmeiner

  DOI：10.1002/cmdc.201200376

  日期：2013.1

  gain metabolic stability. The peptide–peptoid hybrid 2 b showed excellent NTS2 binding affinity (Ki=2.8 nM) and 22 000‐fold selectivity over NTS1, as well as metabolic stability over 32 h in a serum degradation assay. Employing a MAPK‐driven luciferase reporter gene assay and an IP accumulation assay, the neurotensin mimetic 2 b displayed respective inhibitions of constitutive activity exceeding 4.3‐

  亚型选择性神经降压素受体2（NTS2）配体可用作分子探针，以研究神经降压能系统的生理作用，并作为先导化合物来启动开发用于治疗强直性疼痛的药物。从我们最近描述的NTS2配体1开始，合成了2型结构变体，以进一步提高结合亲和力和选择性以获得代谢稳定性。肽-类肽杂化物2b显示出出色的NTS2结合亲和力（K i = 2.8 n M）和NTS1的22,000倍选择性以及血清降解试验中超过32小时的代谢稳定性。通过使用MAPK驱动的萤光素酶报告基因和IP积累测定法，神经降压素模拟物2b分别显示出比内源性配体神经降压素的反向激动剂活性高4.3倍和3.9倍的抑制作用。
• The Effects of C-Terminal Modifications on the Opioid Activity of [<i>N</i>-BenzylTyr¹]Dynorphin A-(1−11) Analogues
  作者：Kshitij A. Patkar、Thomas F. Murray、Jane V. Aldrich

  DOI：10.1021/jm900715m

  日期：2009.11.12

  peptide dynorphin (Dyn) A have focused on the N-terminal “message” sequence based on the “message-address” concept. To test the hypothesis that changes in the C-terminal “address” domain could affect efficacy, modified amino acids and cyclic constraints were incorporated into this region of the partial agonist [N-benzylTyr1]Dyn A-(1−11). Modifications in the C-terminal domain of [N-benzylTyr1]Dyn A-(1−11)NH2

  影响内源性阿片肽强啡肽 (Dyn) A 类似物功效的结构修饰侧重于基于“消息地址”概念的 N 端“消息”序列。为了检验 C 端“地址”结构域的变化可能影响功效的假设，将修饰的氨基酸和循环约束并入部分激动剂 [ N- benzylTyr 1 ]Dyn A-(1-11) 的该区域。[ N- benzylTyr 1 ]Dyn A-(1−11)NH 2的 C 端结构域中的修饰导致所有线性类似物的 κ 阿片受体 (KOR) 亲和力增加，但不影响这些肽在韩国。位置 5 和 8 之间的环化产生 [ N-benzylTyr 1 , cyclo ( d -Asp 5 ,Dap 8 )]Dyn A-(1−11)NH 2 (zyklophin, 13 ) ( J. Med. Chem. 2005 , 48 , 4500−4503) 对 KOR 具有高选择性. 与线性肽相比，该肽在腺苷酸环化酶 (AC) 测定中的功效可忽略不计，并且是
• Impact of the Proline Residue on Ligand Binding of Neurotensin Receptor 2 (NTS2)-Selective Peptide-Peptoid Hybrids
  作者：Cornelia Held、Harald Hübner、Ralf Kling、Yvonne A. Nagel、Helma Wennemers、Peter Gmeiner

  DOI：10.1002/cmdc.201300054

  日期：2013.5

  investigate the binding mode and structure–activity relationships (SARs) of selective neurotensin receptor 2 (NTS2) ligands, novel peptide–peptoid hybrids that simulate the function of the endogenous ligand were developed. Starting from our recently described NTS2 ligands of type 1, structural variants of type 2 and the metabolically stable analogues 3 a,b were developed. Replacement of the proline unit by

  为了研究选择性神经降压素受体2（NTS2）配体的结合模式和结构-活性关系（SAR），开发了模拟内源性配体功能的新型肽-类肽杂化物。从我们最近描述的1型NTS2配体开始，开发了2型的结构变异体和代谢稳定的类似物3a，b。脯氨酸单元被一组结构替代物替代，并对相应分子探针的NTS2亲和力和选择性进行了评估，表明与结合至亚型NTS1的NT（8-13）衍生物所描述的SAR相似。肽-类肽杂种2 d，3 a，b与NTS1相比，具有显着的NTS2结合亲和力（K i = 8.1–16 n M）和2400-8600倍的选择性。噻唑烷衍生物3b在血清降解试验中显示出超过32小时的代谢稳定性。在肌醇磷酸盐积累测定中，神经降压素模拟物3a和3b表现出的组成性活性抑制作用是NT（8-13）活性的1.7-2.0倍。氟化衍生物3a可以提供诱人的机会，通过19 F磁共振成像检测NTS2 。
• Optimizing PEG-Extended Apelin Analogues as Cardioprotective Drug Leads: Importance of the KFRR Motif and Aromatic Head Group for Improved Physiological Activity
  作者：Conrad Fischer、Tess Lamer、Kleinberg Fernandez、Mahmoud Gheblawi、Wang Wang、Cameron Pascoe、Gareth Lambkin、Xavier Iturrioz、Catherine Llorens-Cortes、Gavin Y. Oudit、John C. Vederas

  DOI：10.1021/acs.jmedchem.0c01395

  日期：2020.10.22

  Apelin is an important contributor to the renin-angiotensin axis, regulating cardiovascular, metabolic, and neurological functions. Apelin-17 has especially potent cardio-physiological effects but is rapidly degraded in human blood (t_0.5 ∼ 4 min). Angiotensin-converting enzyme 2 (ACE-2), neprilysin (NEP), and plasma kallikrein (KLKB1) cleave and inactivate it, with the latter cutting within the arginine-arginine site. Here, we show that analogues with an N-terminal polyethylene glycol (PEG) extension as well as peptide bond isosteres resist KLKB1 cleavage but that only the PEG-extended analogues significantly improve physiologically activity. The PEGylated analogues feature comparatively high log D_7.4 values and high plasma protein binding, adding to their stability. An alanine scan of apelin-17 reveals that the integrity and conformational flexibility of the KFRR motif are necessary for cardio-physiological activity. An optimized Cbz-PEG₆ analogue is presented that is stable in blood (t_0.5 ∼ 18 h), has significant blood-pressure lowering effect, and shows fast recovery of heart function in Langendorff assay.
• Improved radiosynthesis and preliminary in vivo evaluation of a 18F-labeled glycopeptide–peptoid hybrid for PET imaging of neurotensin receptor 2
  作者：Simone Maschauer、Cornelia Greff、Jürgen Einsiedel、Julian Ott、Philipp Tripal、Harald Hübner、Peter Gmeiner、Olaf Prante

  DOI：10.1016/j.bmc.2015.01.053

  日期：2015.7

  The neurotensin receptor 2 (NTS2) is an attractive target for cancer imaging, as it is overexpressed in a variety of tumor types including prostate, pancreas and breast carcinoma. The aim of this study was the development of the first NTS2 subtype selective F-18-labeled radioligand for imaging NTS2 expression in vivo by positron emission tomography (PET). The radiosynthesis of glycopeptoid F-18-4 was realized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), applying the prosthetic group 6-deoxy-6-[F-18]fluoroglucosyl azide for F-18-fluoroglycosylation of the alkyne-terminated NT(8-13) analog Pra-N-Me-Arg-Arg-Pro-N-homo-Tyr-Ile-Leu-OH. The binding affinity of the peptide-peptoid 4 for NTS2 was 7 nM with excellent subtype selectivity over NTS1 (260-fold). In vitro autoradiography studies of rat brain slices confirmed the high selectivity of F-18-4 for NTS2. Biodistribution experiments using HT29 and PC3 tumor-bearing nude mice revealed high renal and only moderate tumor uptake, while PET imaging experiments revealed specific binding of F-18-4 in NTS2-positive tumors. As F-18-4 displayed high stability in vitro but fast degradation in vivo, future work will focus on the development of metabolically more stable NT(8-13) analogs. (C) 2015 Elsevier Ltd. All rights reserved.