Fmoc-L-3-碘苯丙氨酸 | 210282-31-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 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: Fmoc-L-3-碘苯丙氨酸
• 中文别名: FMOC-L-3-碘苯基丙氨酸；Fmoc-L-3-碘苯基丙氨酸；Fmoc-3-碘-L-苯丙氨酸
• 英文名称: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-3-iodo-L-phenylalanine
• 英文别名: (S)-2-((((9H-fluoren-9-yl)methoxy)-carbonyl)amino)-3-(3-iodophenyl)propanoic acid；Fmoc-Phe(3-I)-OH；Fmoc-L-Phe(3-l)-OH；Fmoc-(3-I)Phe-OH；Fmoc-3-iodo-L-phenylalanine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(3-iodophenyl)propanoic acid
• CAS: 210282-31-8
• 化学式: C₂₄H₂₀INO₄
• 分子量: 513.332
• InChiKey: SSKOJXLIQFVOGC-QFIPXVFZSA-N

物化性质

• 沸点：
  674.1±55.0 °C(Predicted)
• 密度：
  1.577±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存温度应保持在0-5°C。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-phe(3-I)-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-phe(3-I)-OH
CAS number: 210282-31-8

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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.
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: C24H20INO4
Molecular weight: 513.3

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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, hydrogen Iodide.

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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-L-3-碘苯丙氨酸 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.92h， 生成
  参考文献：
  名称：

  晚期C（sp3）-H激活后的吻合肽

  摘要：

  尽管装订肽对于药物发现很重要，但仅描述了几种制备交联肽的实际方法；因此，目前可用的钉书针图案的结构多样性受到限制。同时，CH活化已成为使复杂分子功能化的有效方法。尽管关于氨基酸的CH功能化的报道很多，但合成后肽CH修饰的例子很少，几乎只包含C（sp 2）-H活化。本文中，我们报道了钯催化的后期C（sp 3）-H活化方法用于肽装订，提供了前所未有的烃交联。该方法首先用于制备溶液中的固定肽文库。研究了与各种氨基酸的相容性以及钉的大小（i，i +3和i，i +4）和长度的影响。最后，还建立了一个简单的固相程序。

  DOI：

  10.1002/anie.201608648
• 作为产物：
  描述：

  1,1-dimethylethyl N-[(9H-fluoren-9-ylmethoxy)carbonyl]-3-iodo-L-phenylalaninate 在 三氟乙酸 作用下， 以93%的产率得到Fmoc-L-3-碘苯丙氨酸
  参考文献：
  名称：

  Enantiomeric enrichment of α-amino acid derivatives: recrystallization of N-Fmoc α-amino acid tert-butyl esters

  摘要：

  The optical purity of products derived from enantioselective reactions of the benzophenone imine of glycine tert-butyl esters can often be improved by conversion to the N-Fmoc alpha -amino acid tert-butyl esters followed by simple recrystallization. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)00554-3

文献信息

• Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
  作者：Wioletta Rut、Marcin Poręba、Paulina Kasperkiewicz、Scott J. Snipas、Marcin Drąg

  DOI：10.1021/acs.jmedchem.8b00026

  日期：2018.6.28

  the HyCoSuL approach, we designed and synthesized novel and selective fluorogenic substrates for each of these three constitutive 20S proteasome activities and applied them to assess inhibition of proteasome subunits by MG-132 and a clinically used inhibitor bortezomib. Our results confirm the utility of designed substrates in biochemical assays. Furthermore, selective peptide sequences obtained in this

  蛋白酶体是维持蛋白质稳态的关键酶复合物。蛋白酶体功能紊乱导致包括癌症，自身免疫和神经退行性疾病在内的病理。因此，蛋白酶体构成药物开发的极好的分子靶标。在这里，我们使用HyCoSuL方法为这三个20S组成型蛋白酶体活性中的每一个设计和合成了新颖的选择性荧光底物，并将它们应用于评估MG-132和临床使用的硼替佐米对蛋白酶体亚基的抑制作用。我们的结果证实了设计的底物在生化分析中的实用性。此外，以此方式获得的选择性肽序列用于构建荧光团标记的基于活性的探针，然后用于同时检测HEK-293F细胞和红细胞裂解液中的每个20S组成型蛋白酶体亚基。总体而言，我们描述了一种简单而快速的方法，可用于测量全血样本中20S组成型蛋白酶体的活性，该方法可以早期诊断与异常上调的蛋白酶体活性有关的病理状态。
• Construction of Natural-Product-Like Cyclophane-Braced Peptide Macrocycles via sp³ C–H Arylation
  作者：Bo Li、Xinghua Li、Boyang Han、Zhijie Chen、Xuekai Zhang、Gang He、Gong Chen

  DOI：10.1021/jacs.9b04221

  日期：2019.6.12

  structures. Herein, we report a generally applicable method for synthesis of natural-product-like cyclophane-braced peptide macrocycles via Pd-catalyzed intramolecular C(sp3)-H arylation with aryl iodides at the remote γ position of various N-terminal aliphatic amino acid units using a simple picolinamide directing group. Products of high structural and stereochemical complexity were quickly assembled

  环肽为探索小分子和生物制剂之间的生物相关化学空间提供了最重要的平台之一。然而，与小分子的设计和合成相比，化学家对环肽三维结构和性质的微调能力远远落后。对环烷肽天然产物很感兴趣，我们想知道刚性、平面和疏水性环烷基序是否可以为合成具有良好 3D 结构的环肽提供新的设计元素。在此处，我们报告了一种普遍适用的合成天然产物样环芳支撑的肽大环化合物的方法，通过 Pd 催化的分子内 C(sp3)-H 芳基化，在各种 N 端脂肪族氨基酸单元的远程 γ 位置使用芳基碘进行芳基化，使用简单的吡啶酰胺导向基团。通过标准固相肽合成制备的易于获得的肽前体快速组装具有高度结构和立体化学复杂性的产品。许多这些肽大环化合物显示出高度有序的结构，正如 X 射线晶体学所揭示的那样。值得注意的是，带有各种游离极性侧链的未受保护肽底物的 PA 导向 C(sp3)-H 环化反应在水性介质中以高效率和选择性进行。
• A Series of Novel, Highly Potent, and Orally Bioavailable Next-Generation Tricyclic Peptide PCSK9 Inhibitors
  作者：Thomas J. Tucker、Mark W. Embrey、Candice Alleyne、Rupesh P. Amin、Alan Bass、Bhavana Bhatt、Elisabetta Bianchi、Danila Branca、Tjerk Bueters、Nicole Buist、Sookhee N. Ha、Mike Hafey、Huaibing He、John Higgins、Douglas G. Johns、Angela D. Kerekes、Kenneth A. Koeplinger、Jeffrey T. Kuethe、Nianyu Li、BethAnn Murphy、Peter Orth、Scott Salowe、Aurash Shahripour、Rodger Tracy、Weixun Wang、Chengwei Wu、Yusheng Xiong、Hratch J. Zokian、Harold B. Wood、Abbas Walji

  DOI：10.1021/acs.jmedchem.1c01599

  日期：2021.11.25

  lowering in cynomolgus monkeys essentially identical to those observed with the clinically approved, parenterally dosed antibodies. These molecules represent the first report of highly potent and orally bioavailable macrocyclic peptide PCSK9 inhibitors with overall profiles favorable for potential development as once-daily oral lipid-lowering agents. In this manuscript, we detail the design criteria and multiparameter

  前蛋白转化酶枯草杆菌蛋白酶样/kexin 9 型 (PCSK9) 是血浆低密度脂蛋白胆固醇 (LDL-C) 的关键调节剂，是治疗高胆固醇血症和冠状动脉疾病的临床验证靶点。从第二代先导结构如2开始，我们能够改进这些结构以获得极强的双环和三环 PCSK9 抑制肽。44等优化分子在使用启用的制剂给药后，证明了足够的口服生物利用度以维持大鼠和食蟹猴的治疗水平。我们在食蟹猴中证明了靶标参与和 LDL 降低与临床批准的肠胃外给药抗体观察到的基本相同。这些分子代表了高效和口服生物可利用的大环肽 PCSK9 抑制剂的第一份报告，其总体特征有利于作为每日一次口服降脂剂的潜在开发。在这份手稿中，我们详细介绍了这一新型 PCSK9 抑制剂系列的设计标准和多参数优化。
• The Meta-Position of Phe4 in Leu-Enkephalin Regulates Potency, Selectivity, Functional Activity, and Signaling Bias at the Delta and Mu Opioid Receptors
  作者：Robert J. Cassell、Krishna K. Sharma、Hongyu Su、Benjamin R. Cummins、Haoyue Cui、Kendall L. Mores、Arryn T. Blaine、Ryan A. Altman、Richard M. van Rijn

  DOI：10.3390/molecules24244542

  日期：——

  As tool compounds to study cardiac ischemia, the endogenous δ-opioid receptors (δOR) agonist Leu5-enkephalin and the more metabolically stable synthetic peptide (d-Ala2, d-Leu5)-enkephalin are frequently employed. However, both peptides have similar pharmacological profiles that restrict detailed investigation of the cellular mechanism of the δOR’s protective role during ischemic events. Thus, a need remains for δOR peptides with improved selectivity and unique signaling properties for investigating the specific roles for δOR signaling in cardiac ischemia. To this end, we explored substitution at the Phe4 position of Leu5-enkephalin for its ability to modulate receptor function and selectivity. Peptides were assessed for their affinity to bind to δORs and µ-opioid receptors (µORs) and potency to inhibit cAMP signaling and to recruit β-arrestin 2. Additionally, peptide stability was measured in rat plasma. Substitution of the meta-position of Phe4 of Leu5-enkephalin provided high-affinity ligands with varying levels of selectivity and bias at both the δOR and µOR and improved peptide stability, while substitution with picoline derivatives produced lower-affinity ligands with G protein biases at both receptors. Overall, these favorable substitutions at the meta-position of Phe4 may be combined with other modifications to Leu5-enkephalin to deliver improved agonists with finely tuned potency, selectivity, bias and drug-like properties.

  作为研究心脏缺血的工具化合物，内源性δ-阿片受体（δOR）激动剂Leu5-恩啡啶和更具代谢稳定性的合成肽（d-Ala2，d-Leu5）-恩啡啶经常被使用。然而，这两种肽具有类似的药理特性，限制了对δOR在缺血事件中保护作用的细胞机制进行详细研究。因此，需要具有改进选择性和独特信号特性的δOR肽，以便研究心脏缺血中δOR信号的特定作用。为此，我们探索了Leu5-恩啡啶的Phe4位置的取代物对调节受体功能和选择性的能力。评估了肽对δOR和µ-阿片受体（µOR）的结合亲和力以及抑制cAMP信号和招募β-阻滞蛋白2的效力。此外，还测量了肽在大鼠血浆中的稳定性。通过在Leu5-恩啡啶的Phe4的间位进行取代，提供了具有不同选择性和偏向性水平的高亲和力配体，同时改善了肽的稳定性，而用吡啶衍生物进行取代则产生了在两种受体上具有G蛋白偏向性的亲和力较低的配体。总的来说，Phe4的间位的这些有利取代物可以与Leu5-恩啡啶的其他修饰结合，提供具有精心调节的效力、选择性、偏向性和药物样性质的改进激动剂。
• [EN] RADIOLABELED COMPOUNDS TARGETING THE PROSTATE-SPECIFIC MEMBRANE ANTIGEN<br/>[FR] COMPOSÉS RADIOMARQUÉS CIBLANT L'ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE
  申请人：PROVINCIAL HEALTH SERVICES AUTHORITY

  公开号：WO2020252598A1

  公开（公告）日：2020-12-24

  A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula or of a salt or a solvate thereof. R0 is O or S. Each of R1a, R1b and R1c may be –CO2H, –SO2H, –SO3H, –PO2H, or –PO3H2, for example. R2 may be methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene, optionally substituted. R3 is a linker. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases/conditions.

  一种化合物，包括以下结构式或其盐或溶剂化合物的前列腺特异性膜抗原（PSMA）靶向基团。R0为O或S。R1a、R1b和R1c中的每一个可以是-CO2H、-SO2H、-SO3H、-PO2H或-PO3H2，例如。R2可以是亚甲基或其衍生物、丙烯基或其衍生物，或乙烯的衍生物，可选择性地取代。R3是一个连接基。当PSMA靶向基团与放射标记基团连接时，该化合物可用作PSMA表达疾病/病况的成像剂或治疗剂。