Fmoc-β³-HLys | 357271-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-β³-HLys
• 英文别名: (3S)-7-Amino-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]heptanoic acid；(3S)-7-amino-3-(9H-fluoren-9-ylmethoxycarbonylamino)heptanoic acid
• CAS: 357271-56-8
• 化学式: C₂₂H₂₆N₂O₄
• 分子量: 382.459
• InChiKey: QXKBUEUYUMTLIE-HNNXBMFYSA-N

物化性质

• 沸点：
  618.4±55.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,3-二-BOC-2-(三氟甲基磺酰)胍 、 Fmoc-β³-HLys 在 N-甲基-N-(三甲基硅烷基)三氟乙酰胺 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到N6-[二[[叔丁氧羰基]氨基]亚甲基]-N2-[芴甲氧羰基]-L-赖氨酸
  参考文献：
  名称：

  Helix formation and capping energetics of arginine analogs with varying side chain length

  摘要：

  Arginine (Arg) has been used for recognizing negatively charged biological molecules, cell penetration, and oligosaccharide mass signal enhancement. The versatility of Arg has inspired the need to develop Arg analogs and to research the structural effects of incorporating Arg analogs. Accordingly, we investigated the effect of Arg side chain length on helix formation by studying 12 Ala-based peptides containing the Arg analogs (S)-2-amino-6-guanidino-hexanoic acid (Agh), (S)-2-amino-4-guanidinobutyric acid (Agb), and (S)-2-amino-3-guanidinopropionic acid (Agp). Solid phase guanidinylation with orthogonal protection strategies was necessary to synthesize Agb- and Agp-containing peptides using Fmoc-based chemistry. The fraction helix for the peptides was determined by circular dichroism spectroscopy, and used to derive the statistical mechanical parameters and energetics for N-capping, C-capping, and helix propagation (propensity). All four Arg analogs were unfavorable for N-capping. The C-cap parameter followed the trend Agp < Agb < Arg < Agh, showing more favorable C-cap energetics with increasing side chain length. In contrast, helix propensity followed the trend Agp < Agb < Arg > Agh, highlighting the uniqueness of the Arg side chain length in helix formation. Molecular mechanics calculations and a survey on protein structures were consistent with the experimental results. Furthermore, calculations and survey both showed that the g- conformation for the chi(1) dihedral was present for the first two residues at the N-terminus of helices, but not favored in the center or C-terminus of helices due to sterics. These results should serve as the foundation for developing Arg-related bioactive compounds and technologies.

  DOI：

  10.1007/s00726-011-1064-2

文献信息

• De Novo Design, Synthesis, and Characterization of Antimicrobial β-Peptides
  作者：Dahui Liu、William F. DeGrado

  DOI：10.1021/ja0107475

  日期：2001.8.1

  against human erythrocytes. Operating under the assumption that their lack of specificity arose from excessive hydrophobicity, two additional β-peptides H-(β3-HAla-β3-HLys-β3-HVal)n-NH2 (n = 4, 5) were designed and synthesized. Both have high antimicrobial activities, but very low hemolytic potencies. The peptides bind in an L+2 conformation to phospholipid vesicles, inducing leakage of entrapped small molecules

  β-肽是一类已被证明具有多种螺旋构象的聚酰胺。最近，设计了一系列两亲性 L+2 螺旋 β-肽，旨在模拟一类膜活性抗菌肽的整体理化特性，包括 magainin 和 cecropin。虽然这些肽显示出有效的抗菌活性，但它们也显示出对人类红细胞的显着活性。假设它们缺乏特异性是由于过度的疏水性引起的，设计和合成了两个额外的 β-肽 H-(β3-HAla-β3-HLys-β3-HVal)n-NH2 (n = 4, 5)。两者都具有高抗微生物活性，但溶血效力非常低。这些肽以 L+2 构象与磷脂囊泡结合，导致被捕获的小分子泄漏。
• On the Influence of Charged Side Chains on the Folding–Unfolding Equilibrium of β-Peptides: A Molecular Dynamics Simulation Study
  作者：Alice Glättli、Xavier Daura、Pascal Bindschädler、Bernhard Jaun、Yogesh R. Mahajan、Raveendra I. Mathad、Magnus Rueping、Dieter Seebach、Wilfred F. van Gunsteren

  DOI：10.1002/chem.200401129

  日期：2005.12.9

  The influence of charged side chains on the folding-unfolding equilibrium of beta-peptides was investigated by means of molecular dynamics simulations. Four different peptides containing only negatively charged side chains, positively charged side chains, both types of charged side chains (with the ability to form stabilizing salt bridges) or no charged side chains were studied under various conditions

  通过分子动力学模拟研究了带电侧链对β-肽折叠-折叠平衡的影响。在各种条件（不同的模拟温度，起始结构和溶剂）下研究了四种仅包含带负电荷的侧链，带正电荷的侧链，两种类型的带电荷的侧链（具有形成稳定的盐桥的能力）或不带电荷的侧链的四种不同肽段环境）。其中一种肽（A）在甲醇中的NMR溶液结构已经公布；本文描述了另一种肽（B）的合成和NMR分析。迄今尚未合成本文研究的其他肽（C和D）。预期所有四种肽AD在溶液中以及在模拟中均采用左手3（14）-螺旋。根据肽采样的构象空间，折叠行为，结构性质（例如氢键，侧链-侧链和侧链-主链相互作用）以及与NMR数据的一致性水平，分析了所得的结构整体可用于其中两种肽。已经发现，由于具有侧链-主链相互作用的中间构象异构体的稳定，带电侧链的存在显着减慢了甲醇溶液中的折叠过程。在水中，溶剂与溶质-溶质极性相互作用竞争，在模拟中向3（14）-螺旋的折叠过程更快。侧链-侧链和侧
• β2/β3-di- and α/β3-tetrapeptide derivatives as potent agonists at somatostatin sst4 receptors
  作者：Caroline Nunn、Magnus Rueping、Daniel Langenegger、Edi Schuepbach、Thierry Kimmerlin、Peter Micuch、Konstanze Hurth、Dieter Seebach、Daniel Hoyer

  DOI：10.1007/s00210-002-0673-4

  日期：2003.2

  Four linear beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptides (1-4) were investigated as somatostatin sst(4) receptor agonists on recombinant human and mouse somatostatin receptors. Human somatostatin receptor subtypes 1-5 (sst(1-5)), and mouse somatostatin receptor subtypes 1,3,4 and 5, were characterised using the agonist radioligands [I-125]LTT-SRIF-28, [I-125][Tyr(10)]CST14 and [I-125]CGP 23996 in stably transfected Chinese hamster lung fibroblast (CCL39) cells. The peptides bound selectively to sst4 receptors with nanomolar affinity (pK(d)=5.4-7.8). The peptides were investigated on second messenger systems both as agonists, and as antagonists to SRIF-14-mediated effects in CCL39 cells expressing mouse sst(4) receptors, via measurement of inhibition of forskolin-stimulated adenylate cyclase activity, and stimulation of luciferase expression. The peptides showed full agonism or pronounced partial agonism (40 to 100% relative intrinsic activity) in both inhibition of forskolin-stimulated adenylate cyclase activity (pEC(50)=5.5-6.8), and luciferase expression (pEC(50)=5.5-6.5). The agonist potential was confirmed since antagonism was very difficult to establish. The data show that beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives have agonist potential at recombinant somatostatin sst(4) receptors. Therefore, they may be used to elucidate physiological and biochemical effects mediated by sst(4), and may also have potential as therapeutic agents.
• Short peptide pharmacophores developed from protein phosphatase-1 disrupting peptides (PDPs)
  作者：Miriam Fontanillo、Malgorzata Trebacz、Christopher D. Reinkemeier、Daniela Avilés Huerta、Ulrike Uhrig、Peter Sehr、Maja Köhn

  DOI：10.1016/j.bmc.2022.116785

  日期：2022.7