Fmoc-(S)-3-aminopentanoic acid | 1303993-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-(S)-3-aminopentanoic acid
• 英文别名: (S)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-pentanoic acid；(3S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoic acid
• CAS: 1303993-81-8
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: RUDHGDWNJABZLC-ZDUSSCGKSA-N

物化性质

• 沸点：
  562.2±33.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Fmoc-(S)-3-aminopentanoic acid 、 NΒ-芴甲氧羰基-NΩ-叔丁氧羰基-L-Β-高赖氨酸 、 N-芴甲氧羰基-(1S,2S)-2-氨基环己烷羧酸 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
  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

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。
• Hydrophobicity and Helicity Regulate the Antifungal Activity of 14-Helical β-Peptides
  作者：Myung-Ryul Lee、Namrata Raman、Samuel H. Gellman、David M. Lynn、Sean P. Palecek

  DOI：10.1021/cb500203e

  日期：2014.7.18

  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.