Nβ-Fmoc-Nω-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-β-高精氨酸 | 700377-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: Nβ-Fmoc-Nω-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-β-高精氨酸
• 中文别名: N_β-Fmoc-N_ω-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-β-高精氨酸；NΒ-FMOC-NΩ-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-Β-高精氨酸；8-五甲基色满-6-磺酰基)-L-Β-高精氨酸
• 英文名称: Fmoc-Nω-(2,2,5,7,8-pentamethylchromane-6-sulfonyl)-L-β-homoarginine
• 英文别名: Fmoc-β³HArg(Pmc)-OH；Fmoc-β-homoArg(Pmc)-OH；Fmoc-β(3)hArg(Pmc)-OH；(3S)-6-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-3-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid
• CAS: 700377-76-0
• 化学式: C₃₆H₄₄N₄O₇S
• 分子量: 676.834
• InChiKey: MGKMEQWQKICWRD-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-芴甲氧羰基-(1S,2S)-2-氨基环己烷羧酸 、 Nβ-Fmoc-Nω-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-β-高精氨酸 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.3h， 生成 (1S,2S)-2-amino-N-[(1S,2S)-2-[[(3S)-1-[[(1S,2S)-2-[[(1S,2S)-2-[[(3S)-1-[[(1S,2S)-2-[[(1S,2S)-2-[[(3S)-1-amino-6-(diaminomethylideneamino)-1-oxohexan-3-yl]carbamoyl]cyclohexyl]carbamoyl]cyclohexyl]amino]-6-(diaminomethylideneamino)-1-oxohexan-3-yl]carbamoyl]cyclohexyl]carbamoyl]cyclohexyl]amino]-6-(diaminomethylideneamino)-1-oxohexan-3-yl]carbamoyl]cyclohexyl]cyclohexane-1-carboxamide
  参考文献：
  名称：

  Hydrophobicity and Helicity Regulate the Antifungal Activity of 14-Helical β-Peptides

  摘要：

  Candida albicans is one of the most prevalent fungal pathogens, causing both mucosal candidiasis and invasive candidemia. Antimicrobial peptides (AMPs), part of the human innate immune system, have been shown to exhibit antifungal activity but have not been effective as pharmaceuticals because of low activity and selectivity in physiologically relevant environments. Nevertheless, studies on a-peptide AMPs have revealed key features that can be designed into more stable structures, such as the 14-helix of beta-peptide-based oligomers. Here, we report on the ways in which two of those features, hydrophobicity and helicity, govern the activity and selectivity of 14-helical beta-peptides against C. albicans and human red Hood cells. Our results reveal both antifungal activity and hemolysis to correlate to hydrophobicity, with intermediate levels of hydrophobicity leading to high antifungal activity and high selectivity toward C. albicans. Helical structure-forming propensity further influenced this window of selective antifungal activity, with more stable helical structures eliciting specificity for C. albicans over a broader range of hydrophobicity. Our findings also reveal cooperativity between hydrophobicity and helicity in regulating antifungal activity and specificity. The results of this study provide critical insight into the ways in which hydrophobicity and helicity govern the activity and specificity of AMPs and identify criteria that may be useful for the design of potent and selective antifungal agents.

  DOI：

  10.1021/cb500203e
• 作为产物：
  描述：

  在 N-甲基吗啉 、 silver trifluoroacetate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 22.5h， 以50%的产率得到Nβ-Fmoc-Nω-(2,2,5,7,8-五甲基色满-6-磺酰基)-L-β-高精氨酸
  参考文献：
  名称：

  Selective Binding of TAR RNA by a Tat-Derived β-Peptide

  摘要：

  The interaction between the HIV-1 Tat protein and the TAR RNA element in the nascent viral genomic transcript is required for viral replication. An 11-residue beta-peptide (1), an all-beta homologue of the Arg-rich region Tat 47-57, binds TAR RNA with K-d = 29 +/- 4 nM. A control beta-peptide (2) in which all Arg side chains are replaced by Lys side chains shows increased affinity but decreased specificity for wild-type vs bulge-deleted TAR RNA, as do the alpha-peptide analogues of 1 and 2.

  DOI：

  10.1021/ol034977v

文献信息

• Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species
  作者：Namrata Raman、Myung-Ryul Lee、David Lynn、Sean Palecek

  DOI：10.3390/ph8030483

  日期：——

  Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics.

  白色念珠菌是真菌感染最常见的病因，耐药性生物膜的形成（通常在植入式医疗器械表面）使治疗变得更加复杂。近年来，由其他致病性念珠菌（如光滑念珠菌、副丝状念珠菌和热带念珠菌）引起的真菌感染发病率有所上升。天然抗菌剂 α 肽的两亲螺旋 β 肽结构模拟物在体外对白念珠菌表现出特异性浮游抗真菌和抗生物膜形成活性。在这里，我们证明了 β 肽对临床分离的白念珠菌耐药菌株和其他机会性念珠菌属也有活性。不同的念珠菌属对 β 肽有不同程度的易感性，其中热带念珠菌的易感性最高，格拉布氏念珠菌的易感性最低。β肽的疏水性与对所有受试念珠菌临床菌株和菌种的抗真菌活性直接相关。虽然 β 肽对破坏现有的念珠菌生物膜基本无效，但疏水性 β 肽却能阻止白念珠菌、草绿色念珠菌、副丝状念珠菌和热带念珠菌生物膜的形成。β肽对浮游细胞和防止生物膜形成的广谱抗真菌活性表明，这类分子有望成为治疗药物。
• On the Terminal Homologation of Physiologically Active Peptides as a Means of Increasing Stability in Human Serum - Neurotensin, Opiorphin, B27-KK10 Epitope, NPY
  作者：Dieter Seebach、Aneta Lukaszuk、Krystyna Patora-Komisarska、Dominika Podwysocka、James Gardiner、Marc-Olivier Ebert、Jean Claude Reubi、Renzo Cescato、Beatrice Waser、Peter Gmeiner、Harald Hübner、Catherine Rougeot

  DOI：10.1002/cbdv.201100093

  日期：2011.5

  With N-terminally homologated NPY, 5c, we were not able to determine serum stability; the peptide consisting of 36 amino acid residues is subject to cleavage by endopetidases. Three of the homologated compounds, 2b, 2c, and 5c, were shown to be agonists (Fig. 7 and 11). A comparison of terminal homologation with other stability-increasing terminal modifications of peptides is performed (Fig. 5), and possible

  描述了通过CH（2）插入标题中提及的肽的末端同源性。这涉及用β（2）取代N末端氨基酸残基，以及用β（3）均氨基酸部分（β（2）hXaa和β（3）取代C末端氨基酸残基。 hXaa，分别；图1）。这样，从N末端到C末端立体异构中心的肽链的结构是相同的，并且修饰的肽被保护以免被外肽酶切割（图2和3）。神经降压素（NT; 1）及其C端片段NT（8-13）是G蛋白偶联受体（GPCR）的配体NT1，NT2，NT3和NT类似物是有望用于癌症诊断和治疗的工具治疗。通过使用细胞匀浆和肿瘤组织确定同源的NT类似物2b-2e对NT1和NT2受体的亲和力（表1）；在后面的实验中，NT1受体的亲和力与NT大致相同（0.5-1.3对0.6 nM）。同时，同源的NT类似物之一2c在人血浆中在37°下存活7天（图6）。NT（8-13）的NMR分析（表2和4，以及图8）显示，该N端NT片段折叠成CD（3）OH。-对于人镇痛
• Design, Synthesis and Structural Investigations of aβ-Peptide Forming a 314-Helix Stabilized by Electrostatic Interactions
  作者：Magnus Rueping、Yogesh R. Mahajan、Bernhard Jaun、Dieter Seebach

  DOI：10.1002/chem.200305571

  日期：2004.4.2

  different strategies have been employed for the synthesis of Fmoc-protected beta(3)-homoarginine; the Arndt-Eistert homologation of alpha-arginine and the guanidinylation of beta(3)-homoornithine. Solid-phase beta-peptide synthesis was used for the preparation of beta-heptapeptide 1, which was designed to form a helix stabilized by electrostatic interactions through positively (beta(3)hArg) and negatively

  两种不同的策略已被用于合成Fmoc保护的beta（3）-homo精氨酸。α-精氨酸的Arndt-Eistert同源性和β（3）-高鸟氨酸的胍基化。固相β-肽合成用于制备β-七肽1，该肽被设计为形成通过正电荷（β（3）hArg）和负电荷（β（3）hGlu）静电相互作用稳定的螺旋结构残留物。CD测量和相应的MeOH和水溶液中的NMR研究确实表明，β-肽3（14）-螺旋可以通过盐桥形成而稳定。
• Modulators of C3a receptor and methods of use thereof
  申请人：Biediger Ronald J.

  公开号：US20080188528A1

  公开（公告）日：2008-08-07

  Provided are compounds that are modulators of C3a receptor activity, compositions containing the compounds and methods of use of the compounds and compositions. In certain embodiments, the compounds are pyridones. In certain embodiments, provided are methods for treatment or amelioration of diseases associated with modulation of C3a receptor activity.

  提供了一些化合物，它们是C3a受体活性的调节剂，包括含有这些化合物的组合物和使用这些化合物和组合物的方法。在某些实施例中，这些化合物是吡啶酮。在某些实施例中，提供了用于治疗或改善与C3a受体活性调节相关的疾病的方法。
• Peptide backbone modifications on the C-terminal hexapeptide of neurotensin
  作者：Jürgen Einsiedel、Harald Hübner、Maud Hervet、Steffen Härterich、Susanne Koschatzky、Peter Gmeiner

  DOI：10.1016/j.bmcl.2008.01.110

  日期：2008.3

  To compare backbone-induced susceptibilities with affinity changes that are caused by side-chain modifications in the respective positions, structure activity relationship studies on a series of NT(8-13) analogues were performed providing valuable insights into the major requirement for neurotensin receptor recognition and activation. The data led us to highly potent NTR1 ligands and the generation of a pharmacophore model that will be helpful for the discovery of therapeutically relevant non-peptidic NTR1 agonists. (C) 2008 Elsevier Ltd. All rights reserved.