马脲酰组氨酰亮氨酸HHL | 31373-65-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 亮氨酸类衍生物
• 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: 马脲酰组氨酰亮氨酸HHL
• 中文别名: 马脲酰-L-组氨酰-L-亮氨酸四水合物；马脲酰组氨酰亮氨酸
• 英文名称: hippuryl-L-histidyl-L-leucine
• 英文别名: hippuryl-histidyl-leucine；HHL；Hip-His-Leu；(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoic acid
• CAS: 31373-65-6
• 化学式: C₂₁H₂₇N₅O₅
• 分子量: 429.476
• InChiKey: AAXWBCKQYLBQKY-IRXDYDNUSA-N

物化性质

• 沸点：
  912.4±65.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)
• 溶解度：
  乙酸：50 mg/mL，澄清，无色
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，也未有已知危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  153
• 氢给体数：
  5
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

SDS

Name:	Hippuryl-L-Histidyl-L-Leucine Tetrahydrate 99% Material Safety Data Sheet
Synonym:	None known
CAS:	31373-65-6

Section 1 - Chemical Product MSDS Name:Hippuryl-L-Histidyl-L-Leucine Tetrahydrate 99% Material Safety Data Sheet
Synonym:None known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
31373-65-6	Hippuryl-L-Histidyl-L-Leucine Tetrahyd	99	250-597-9

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up, then place into a suitable container for disposal. Avoid generating dusty conditions. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Deep freeze (below -20C).

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 31373-65-6: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 150.00 - 155.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C21H27N5O5.4H2O
Molecular Weight: 501.50

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 31373-65-6 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Hippuryl-L-Histidyl-L-Leucine Tetrahydrate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 31373-65-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 31373-65-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 31373-65-6 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  马脲酰组氨酰亮氨酸HHL 在 angiotensin converting enzyme 作用下， 以 aq. buffer 为溶剂， 反应 0.83h， 生成 马尿酸
  参考文献：
  名称：

  高效液相色谱-串联四极杆质谱法研究血管紧张素转化酶上苯乙醛糖苷的结构-抑制关系†

  摘要：

  血管紧张素转换酶（ACE）在肾素-血管紧张素系统中起关键作用。最近，从草药中分离出的天然产物已显示出对ACE的抑制作用，表明它们在调节血压方面具有潜在价值。在本研究中，通过使用快速，灵敏，准确和特异的超高效液相色谱-串联四极杆质谱仪测量马尿酸（HA）的生成，研究了由21种苯基乙醛糖苷和相关酚类化合物提供的ACE抑制（ACEI）。光谱分析（UPLC-MS / MS）方法。测试化合物在50 mM时对ACE表现出宽广的抑制效力，范围为5.29％至95.01％，并且选择ICEI大于50％的化合物作为IC 50测定，是一种物质抑制特定生物学功能的有效性的量度。IC 50值的范围为0.53±0.04至15.035±0.036 mM。然后研究了结构-抑制关系，结果表明肉桂酰基在苯乙醛糖苷的ACEI中起着至关重要的作用。此外，苯乙醇类糖苷中ACEI增加的子结构涉及更多的羟基基团和较小的空间位阻，从而允许活性Zn

  DOI：

  10.1039/c5ra05027h
• 作为产物：
  描述：

  马尿酸 、 L-组氨酰-L-亮氨酸 在 angiotensin I converting enzyme 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成 马脲酰组氨酰亮氨酸HHL
  参考文献：
  名称：

  Novel Fluorogenic substrates containing Bimane system for microdetermination of angiotensin I converting enzyme.

  摘要：

  作为一种灵敏的荧光分析法，用于检测血管紧张素转化酶活性的含吲哚乙酸的联苯胺肽，即1, 7-二氧-2, 5, 6-三甲基-1H, 7H, 吡唑[1, 2-α]吡唑-3-基-甲硫甲酰基-甘氨酰(或L-苯丙氨酰)-L-色氨酰-L-亮氨酸(或L-脯氨酸)，已被合成，并被证明是用于微量测定血管紧张素I转化酶活性的强效荧光底物。

  DOI：

  10.1248/cpb.37.145

文献信息

• Compositions and Methods Comprising Carboxylic Acid-Containing Small Molecules
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US20150087605A1

  公开（公告）日：2015-03-26

  Disclosed are compositions and methods for treating anthrax, inhibiting anthrax toxins and inhibiting anthrax toxin-induced cytotoxicity. Carboxylic acid-containing small molecules can be used in the methods and compositions disclosed herein, for example, sulindac and derivatives thereof may be used. Methods of screening for carboxylic acid-containing small molecules that can be used to treat anthrax are disclosed. Targeting the anthrax toxin reduces the risks of anthrax spores.

  本文揭示了用于治疗炭疽病、抑制炭疽毒素以及抑制炭疽毒素诱导的细胞毒性的组合物和方法。可以在此披露的方法和组合物中使用含有羧酸的小分子，例如，可以使用硫酸卢卡因和其衍生物。还披露了筛选可用于治疗炭疽病的含有羧酸的小分子的方法。针对炭疽毒素可以降低炭疽孢子的风险。
• Enzyme Inhibitor Screening by Capillary Electrophoresis with an on-Column Immobilized Enzyme Microreactor Created by an Ionic Binding Technique
  作者：Zhong-mei Tang、Jing-wu Kang

  DOI：10.1021/ac052030w

  日期：2006.4.1

  strategy for screening the enzyme inhibitors from the complex mixtures by capillary electrophoresis with an on-column immobilized enzyme microreactor created by an ionic binding technique is reported. The enzyme microreactor was prepared in two steps: First, the capillary wall was dynamically coated with a polycationic electrolyte hexadimethrine bromide (HDB) by simply flushing the column using the HDB

  报导了一种新的策略，该方法可通过毛细管电泳与离子结合技术产生的柱上固定酶微反应器进行毛细管电泳，从复杂混合物中筛选酶抑制剂。酶微反应器分两步制备：首先，通过简单地使用HDB溶液冲洗色谱柱，在毛细管壁上动态涂上聚阳离子电解质溴化己二酸二丁酯（HDB）。随后，注入酶溶液的塞子并孵育5分钟，以使酶分子通过离子结合固定在带正电荷的涂层上。为了证明该策略，将血管紧张素转化酶（ACE）用作酶固定，抑制研究和抑制剂筛选的模型。已经证明，这种制备的固定化ACE微反应器显示出足够高的活性和稳定性。此外，固定的酶微反应器可以容易地更新。通过以下步骤完成抑制研究或抑制剂筛选：（i）将底物溶液注入微反应器中并在短时间内孵育；（ii）随后，基于其不同的迁移率，施加电压以将酶反应的产物与未反应的底物分离，产物的峰面积代表酶的活性；（iii）将一定量的酶抑制剂或候选化合物掺入底物溶液中，以测定固定化酶活性的降低。因此，
• TRIPEPTIDE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
  申请人：NORTHWEST UNIVERSITY

  公开号：US20170267718A1

  公开（公告）日：2017-09-21

  Provided are a tripeptide compound, a preparation method therefor, and an application thereof. The structure of the related compound is represented by formula (I). The provided compound has angiotensin converting enzyme inhibiting bioactivity, and the compound and a pharmaceutical composition thereof play a role in preventing and treating hypertension and other cardiocerebral vascular system diseases.

  提供了一种三肽化合物，其制备方法和应用。相关化合物的结构由式（I）表示。提供的化合物具有抑制血管紧张素转换酶的生物活性，该化合物及其药物组成对预防和治疗高血压和其他心脑血管系统疾病起着作用。
• Histidine-Directed Arylation/Alkenylation of Backbone N–H Bonds Mediated by Copper(II)
  作者：Jun Ohata、Matthew B. Minus、Morgan E. Abernathy、Zachary T. Ball

  DOI：10.1021/jacs.6b03390

  日期：2016.6.22

  Chemical modification of proteins and peptides represents a challenge of reaction design as well as an important biological tool. In contrast to side-chain modification, synthetic methods to alter backbone structure are extremely limited. In this communication, copper-mediated backbone N-alkenylation or N-arylation of peptides and proteins by direct modification of natural sequences is described. Histidine

  蛋白质和肽的化学修饰是反应设计的挑战，也是重要的生物学工具。与侧链修饰相比，改变主链结构的合成方法极为有限。在此通讯中，描述了通过直接修饰天然序列，铜介导的主链 N-烯基化或 N-芳基化肽和蛋白质。组氨酸残基在相邻氨基酸的主链 NH 处直接氧化偶联硼酸。在环境温度下，普通生理缓冲液中的温和反应条件与蛋白质和生物系统兼容。这个简单的反应证明了在复杂系统中进行定向反应的潜力，可以修饰直接影响多肽结构、稳定性和功能的 NH 键。
• Pharmaceutically active compounds
  申请人：FISONS plc

  公开号：EP0384636A1

  公开（公告）日：1990-08-29

  There are described compounds of formula I, processes for their preparation and pharmaceutical formulations containing them, ZCHR₁COR₂      I in which R₂ is a group of formula II, -NRxCHRyCOOH      II in which Rx and Ry are each alkyl optionally substituted by phenyl; phenylalkyl C7 to 12, phenyl, phenyloxyalkyl, N-alkyl, O-alkyl, or together Rx and Ry may form a heterocyclic group optionally substituted by alkyl, phenyl; phenylalkyl C7 to 12, phenyl, phenyloxyalkyl, N-alkyl, O-alkyl, or one of Rx and Ry may be hydrogen, provided that one of Rx and Ry, the heterocyclic group formed by Rx and Ry or the optional substituents is substituted by one or two groups -COOR₉ R₉ is phenyl, -(CH₂)xCONR₁₄R₁₅, -(CH₂)yCOOR₁₆ or alkyl optionally substituted by phenyl; R₁₄, R₁₅, R₁₆, x and y, are as described in the specification, and pharmaceutically acceptable salts thereof.

  描述了化合物的公式I，其制备过程和含有它们的制药配方，其中R₂是公式II的一个基团，-NRxCHRyCOOH，在其中Rx和Ry各自是可选择由苯基取代的烷基；苯基烷基C7至12，苯基，苯氧基烷基，N-烷基，O-烷基，或者Rx和Ry可以共同形成一个杂环基团，该基团可选择由烷基、苯基取代；苯基烷基C7至12，苯基，苯氧基烷基，N-烷基，O-烷基，或者Rx和Ry中的一个可以是氢，前提是Rx和Ry中的一个，由Rx和Ry形成的杂环基团或可选择的取代基团之一被一个或两个基团取代，-COOR₉R₉是苯基，-(CH₂)xCONR₁₄R₁₅，-(CH₂)yCOOR₁₆或者可选择由苯基取代的烷基；R₁₄，R₁₅，R₁₆，x和y如规范中所述，并且其药学上可接受的盐。

表征谱图