leucyl-methionine amide hydrochloride | 2131-00-2

• 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
• 英文名称: leucyl-methionine amide hydrochloride
• 英文别名: H-Leu-Met-NH2*HCl；HCl*H-Leu-Met-NH2；HCl*Leu-Met-NH2；Leu-Met-NH2*HCl；(2S)-2-amino-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-4-methylpentanamide;hydrochloride
• CAS: 2131-00-2
• 化学式: C₁₁H₂₃N₃O₂S*ClH
• 分子量: 297.849
• InChiKey: UDQMCHPCASVZSQ-OZZZDHQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  leucyl-methionine amide hydrochloride 在 苯甲醚 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 pyroglutamyl-phenylalanyl-phenylalanine-glycyl-leucyl-methionine amide
  参考文献：
  名称：

  Activity of the C-terminal part of substance P on guinea pig ileum and trachea preparations I. N-acylated pentapeptides SP(7–11)

  摘要：

  DOI：

  10.1016/0223-5234(88)90006-2
• 作为产物：
  描述：

  N-{[(2-甲基-2-丙基)氧基]羰基}-L-亮氨酰-L-蛋氨酸甲酯 在 盐酸 、 氨 作用下， 以 乙酸乙酯 为溶剂， 反应 48.25h， 生成 leucyl-methionine amide hydrochloride
  参考文献：
  名称：

  Lipkowski, Andrzej W.; Misicka, Aleksandra; Drabarek, Stefania, Polish Journal of Chemistry, 1981, vol. 55, # 4, p. 813 - 818

  摘要：

  DOI：

文献信息

• Synthesis of partially modified retro-inverso substance P analogs and their biological activity
  作者：Michael Chorev、Elie Rubini、Chaim Gilon、Uri Wormser、Zvi Selinger

  DOI：10.1021/jm00356a003

  日期：1983.2

  Partial retro-inverso modification of a single peptide bond was applied to pGlu-Phe-Phe-Gly-Leu-Met-NH2 (I), a C-terminal hexapeptide analogue of the neuropeptide substance P. Two analogues with reversed peptide bonds, between the pGlu-Phe and Phe-Gly residues, were prepared, purified and characterized. The analogue gpGlu-(RS)-mPhe-Phe-Gly-Leu-Met-NH2 (II) was devoid of either agonistic or antagonistic

  单肽键的部分逆向逆向修饰应用于pGlu-Phe-Phe-Gly-Leu-Met-NH2（I），这是神经肽物质P的C端六肽类似物。两个具有反向肽键的类似物之间制备，纯化和鉴定pGlu-Phe和Phe-Gly残基。类似物gpGlu-（RS）-mPhe-Phe-Gly-Leu-Met-NH2（II）没有激动或拮抗活性。发现第二种伪肽类似物，即pGlu-Phe-gPhe-mGly-Leu-Met-NH2（III），是完全的激动剂，在豚鼠回肠测定中具有I的22％的效价。
• Synthesis and Biological Evaluation of Dehydrophenylalanine Containing Substance P Fragments
  作者：Paramjeet Kaur、Gyanedra Kumar Patnaik、Ram Raghubir、Virander Singh Chauhan

  DOI：10.1246/bcsj.65.3412

  日期：1992.12

  Peptide fragments of Substance P corresponding to the C-terminal segments (6-11) and (4-11), which contain a putative β-turn, were synthesised using solution phase methodology. Analogs of Substance P were synthesised where the phenylalanine residue at position 8 was replaced by dehydrophenylalanine (ΔPhe) and the glycine residue in position 9 was replaced by alanine, valine, sarcosine (N–Me–Gly) and α-aminoisobutyric acid. In two of the analogs [8-ΔPhe, 9-Sar]–SP (4-11) (5) and [5,8-ΔPhe, 9-Aib]–SP (4-11) (7) glutamine residue at position 5 was also substituted by ΔPhe. These analogs were evaluated for their ability to cause smooth muscle contraction in guinea pig ileum preparation (in vitro) and for hypotensive activity (in vivo) in female rats anesthetized with urethane. In the hexapeptide series [8-ΔPhe]–SP (6-11) (1) and [8-ΔPhe, 9-Sar]–SP (6-11) (4) showed significant activity in both the assays. Octapeptide [5,8-ΔPhe, 9-Sar]–SP (4-11) (5) with ΔPhe residue in positions 5 and 8 and sarcosine in position 9 was found to be the most potent analog both in vitro and in vivo systems.

  合成了与物质P的C端片段（6-11）和（4-11）相对应的肽段，这些片段包含一个假定的β-转角，采用溶液相的方法。合成了物质P的类似物，其中第8位的苯丙氨酸残基被脱氢苯丙氨酸（ΔPhe）替代，第9位的甘氨酸残基被丙氨酸、缬氨酸、肌氨酸（N–Me–Gly）和α-氨基异丁酸替代。在两个类似物[8-ΔPhe, 9-Sar]–SP (4-11) (5)和[5,8-ΔPhe, 9-Aib]–SP (4-11) (7)中，第5位的谷氨酰胺残基也被ΔPhe替代。这些类似物在豚鼠回肠制备中（体外）评估了其引起平滑肌收缩的能力，并在以氨基甲酸酯麻醉的雌性大鼠中评估了其降血压活性。在六肽系列中，[8-ΔPhe]–SP (6-11) (1)和[8-ΔPhe, 9-Sar]–SP (6-11) (4)在两项实验中均显示出显著的活性。八肽[5,8-ΔPhe, 9-Sar]–SP (4-11) (5)在第5和第8位具有ΔPhe残基并在第9位含有肌氨酸，发现其在体外和体内系统中是最有效的类似物。
• Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies
  作者：Constantine Poulos、John R. Brown、Christopher C. Jordan

  DOI：10.1021/jm00157a028

  日期：1986.7

  series of analogues of the C-terminal hexapeptide of substance P, modified at the glutaminyl residue, was synthesized and their relative activities as spasmogens were determined in the guinea pig ileum and rat colon muscularis mucosae preparations in vitro. In general, when compared to SP6-11, the loss of the carboxamide group has little effect on activity in the colon and reduces activity on the ileum

  合成了一系列在谷氨酰胺残基上修饰的物质P的C端六肽类似物，并在体外确定了豚鼠回肠和大鼠结肠粘膜黏膜制剂中作为痉挛源的相对活性。通常，与SP6-11相比，羧酰胺基的丢失对结肠的活性影响很小，而对回肠的活性降低。例外的是Orn6类似物，它在两种制剂中均具有活性，被提议作为结构活性研究的有用工具。结论是6位取代基的氢键电势可能是生物活性的重要决定因素。
• Synthesis and conformation of n-trityl dipeptide derivatives
  作者：J. Matsoukas、Th. Tsegenidis、P. Cordopatis、D. Theodoropoulos

  DOI：10.1016/s0040-4020(01)91142-1

  日期：1984.1

  N-Tritylamino acids activated with DCC/HOBt, were coupled with various amino acid derivatives without racemization. The trityl group was split off quantitatively in 10% CCl3COOH monohydrate or CH2ClCOOH in CH2Cl2. Under these conditions detritylation of N-Trt-Trp-Gly-NH2 proceeds without formation of an oxindole derivative and side alkylation products, even in the absence of a scavenger. Dipeptide

  用DCC / HOBt活化的N-三苯甲基氨基酸与各种氨基酸衍生物偶联而没有外消旋作用。在10％CCl 3 COOH一水合物或CH 2 Cl 2中的CH 2 ClCOOH中将三苯甲基定量分离。在这些条件下，即使不存在清除剂，N-Trt-Trp-Gly-NH 2的去三苯甲基化反应也不会形成羟吲哚衍生物和副烷基化产物。二肽衍生物1和2表现出磁不对称性，归因于空间因素。
• Ketomethylene pseudopeptide analogs of substance P: synthesis and biological activity
  作者：Ariel Ewenson、Ralph Laufer、Michael Chorev、Zvi Selinger、Chaim Gilon

  DOI：10.1021/jm00152a020

  日期：1986.2

  characterized, and tested for their biological activity and inhibitory effect on SP degrading enzymes. Analogue II was a full agonist contracting the isolated guinea pig ileum with a potency of 70% compared to the parent hexapeptide [pGlu6]SP6-11. It was also a potent inhibitor of SP degrading activity in rat diencephalon membranes with a Ki of 20 microM whereas analogue I was a weak inhibitor.

  与P相关的C端的两个假肽类似物[Bz-（RS）Phe8 psi（COCH2）Gly9] SP8-11（I）和[pGlu6，（RS）Phe8 psi（COCH2）Gly9] SP6-11（II）如下制备六肽[pGlu6] SP6-11。伪二肽单元H（RS）Phe psi（COCH2）GlyOH是通过Bz-Phe-OH与单甲基琥珀酰氯之间的修饰的Dakin-West反应合成的。然后通过使用各种偶联方法将Nα-保护的假肽单元掺入适当的肽中。纯化，表征并测试了两种假肽类似物的生物活性以及对SP降解酶的抑制作用。与亲本六肽[pGlu6] SP6-11相比，类似物II是完全的激动剂，可收缩分离的豚鼠回肠，效力为70％。