temporin L | 188713-81-7

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: temporin L
• 英文别名: FVQWFSKFLGRIL-NH₂；(2S)-N-[(2S)-1-[(2S)-1-[(2S)-1-[(2S)-6-amino-1-[(2S)-1-[(2S)-1-[2-[(2S)-5-carbamimidamido-1-hydroxy-1-[(2S,3S)-1-hydroxy-1-[(2S)-1-hydroxy-1-imino-4-methylpentan-2-yl]imino-3-methylpentan-2-yl]iminopentan-2-yl]imino-2-hydroxyethyl]imino-1-hydroxy-4-methylpentan-2-yl]imino-1-hydroxy-3-phenylpropan-2-yl]imino-1-hydroxyhexan-2-yl]imino-1,3-dihydroxypropan-2-yl]imino-1-hydroxy-3-phenylpropan-2-yl]imino-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]-2-[[(2S)-2-[[(2S)-2-amino-1-hydroxy-3-phenylpropylidene]amino]-1-hydroxy-3-methylbutylidene]amino]pentanediimidic acid
• CAS: 188713-81-7
• 化学式: C₈₃H₁₂₂N₂₀O₁₅
• 分子量: 1640.01
• InChiKey: SDXHFGQTTLDWPF-VTKIVCRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  118
• 可旋转键数：
  53
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  585
• 氢给体数：
  21
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  temporin L 、 benzhydryl (5R,6R,7R)-3-((((4-nitrophenoxy)carbonyl)oxy)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  使用 β-内酰胺酶可激活的抗菌肽选择性抑制耐药细菌病原体，细胞毒性显着降低

  摘要：

  β-内酰胺酶，特别是金属-β-内酰胺酶 (MBL) 在细菌中的表达导致了对临床上重要的β-内酰胺类抗生素（包括救命的碳青霉烯类）的显着耐药性。抗菌肽 (AMP) 已成为对抗抗生素耐药性的有前途的治疗剂。然而，细胞毒性 AMP 一直是其在临床实践中应用的主要关注点之一。在此，我们报告了一种新型头孢菌素笼状 AMP，它显示出显着降低的细胞毒性、溶血活性和抗菌活性，但在引起抗菌素耐药性的 β-内酰胺酶特异性水解后，对细菌具有很高的活性。进一步的调查证明了这个β-内酰胺酶可激活的 AMP 选择性地灭活耐药细菌病原体而不是易感细菌。该策略应该适用于其他 AMP，作为治疗由表达β-内酰胺酶的致病菌引起的传染病的潜在解决方案。

  DOI：

  10.1016/j.cclet.2022.107847
• 作为产物：
  描述：

  在 哌啶 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 以6.9 mg的产率得到temporin L
  参考文献：
  名称：

  Photocontrolled Compound Release System Using Caged Antimicrobial Peptide

  摘要：

  A novel photocontrolled compound release system using liposomes and a caged antimicrobial peptide was developed. The caged antimicrobial peptide was activated by UV irradiation, resulting in the formation of pores on the liposome surface to release the contained fluorophores. The compound release could be observed using fluorescence measurements and time-lapse fluorescence microscopy. UV irradiation resulted in a quick release of the inclusion compounds (within 1 min in most cases) under simulated physiological conditions. The proposed system is expected to be applicable in a wide range of fields from cell biology to clinical sciences.

  DOI：

  10.1021/ja102167m

文献信息

• The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin‐L
  作者：Elisabetta Buommino、Alfonso Carotenuto、Ignazio Antignano、Rosa Bellavita、Bruno Casciaro、Maria Rosa Loffredo、Francesco Merlino、Ettore Novellino、Maria Luisa Mangoni、Francesca Paola Nocera、Diego Brancaccio、Pasqualina Punzi、Daniela Roversi、Raffaele Ingenito、Elisabetta Bianchi、Paolo Grieco

  DOI：10.1002/cmdc.201900221

  日期：2019.7.3

  Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro3]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non‐natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities

  以前，我们确定了一种有效的temporin L（TL）抗微生物类似物，[Pro 3] TL，其中第3位的谷氨酰胺被脯氨酸取代。在这项研究中，研究了一系列类似物（其中第3位被非天然脯氨酸衍生物取代）在化合物的构象性质与其抗菌，细胞毒性和溶血活性之间的相关性。有人认为在吡咯烷环第4位带有取代基的非天然脯氨酸类似物。这些类似物的结构-活性关系（SAR）研究是通过抗微生物和细胞毒性测定以及圆二色性（CD）和NMR光谱分析对选定的化合物进行的。此外，还评估了最有前途的多肽对某些代表性兽医微生物菌株的活性，以与人源菌株进行比较。
• Structure−Activity Relationship, Conformational and Biological Studies of Temporin L Analogues
  作者：Maria Luisa Mangoni、Alfonso Carotenuto、Luigia Auriemma、Maria Rosaria Saviello、Pietro Campiglia、Isabel Gomez-Monterrey、Stefania Malfi、Ludovica Marcellini、Donatella Barra、Ettore Novellino、Paolo Grieco

  DOI：10.1021/jm1012853

  日期：2011.3.10

  Temporins are naturally occurring peptides with promising features, which could lead to the development of new drugs. Temporin-ITI (TL) is the strongest antimicrobial peptide, but it is toxic on human erythrocytes and this fact makes the design of synthetic analogues with a higher therapeutic index vital. We studied the structure activity relationships of a library of TL derivatives focusing on the correlation between the a-helix content of the peptides, the nature of their cationic residues, and their antibacterial/antiyeast/hemolytic activities. We found that the percentage of helicity of TL analogues is directly correlated to their hemolytic activity but not to their antimicrobial activity. In addition, we found that the nature of positively charged residues can affect the biological properties of TL without changing the peptide's helicity. It is noteworthy that a single amino acid substitution can prevent the antimicrobial activity of TL, making it a lytic peptide presumably due to its self-association. Last,, we identified a novel analogue with properties that make it an attractive topic for future research.
• CN116850265
  申请人：——

  公开号：——

  公开（公告）日：——
• Photocontrolled Compound Release System Using Caged Antimicrobial Peptide
  作者：Shin Mizukami、Mariko Hosoda、Takafumi Satake、Satoshi Okada、Yuichiro Hori、Toshiaki Furuta、Kazuya Kikuchi

  DOI：10.1021/ja102167m

  日期：2010.7.21

  A novel photocontrolled compound release system using liposomes and a caged antimicrobial peptide was developed. The caged antimicrobial peptide was activated by UV irradiation, resulting in the formation of pores on the liposome surface to release the contained fluorophores. The compound release could be observed using fluorescence measurements and time-lapse fluorescence microscopy. UV irradiation resulted in a quick release of the inclusion compounds (within 1 min in most cases) under simulated physiological conditions. The proposed system is expected to be applicable in a wide range of fields from cell biology to clinical sciences.
• Selective inhibition of resistant bacterial pathogens using a β-lactamase-activatable antimicrobial peptide with significantly reduced cytotoxicity
  作者：Weipan Xu、Zheng Ma、Geetika Dhanda、Jayanta Haldar、Hexin Xie

  DOI：10.1016/j.cclet.2022.107847

  日期：2023.5

  hydrolysis by the antimicrobial resistance-causative β-lactamase. Further investigations demonstrate this β-lactamase-activatable AMP selectively inactivates resistant bacterial pathogens over susceptible bacteria. This strategy should be applicable to other AMPs as a potential solution for the treatment of infectious diseases caused by β-lactamase-expressing pathogenic bacteria.

  β-内酰胺酶，特别是金属-β-内酰胺酶 (MBL) 在细菌中的表达导致了对临床上重要的β-内酰胺类抗生素（包括救命的碳青霉烯类）的显着耐药性。抗菌肽 (AMP) 已成为对抗抗生素耐药性的有前途的治疗剂。然而，细胞毒性 AMP 一直是其在临床实践中应用的主要关注点之一。在此，我们报告了一种新型头孢菌素笼状 AMP，它显示出显着降低的细胞毒性、溶血活性和抗菌活性，但在引起抗菌素耐药性的 β-内酰胺酶特异性水解后，对细菌具有很高的活性。进一步的调查证明了这个β-内酰胺酶可激活的 AMP 选择性地灭活耐药细菌病原体而不是易感细菌。该策略应该适用于其他 AMP，作为治疗由表达β-内酰胺酶的致病菌引起的传染病的潜在解决方案。