N-α-Fmoc-D-Lys allyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-α-Fmoc-D-Lys allyl ester
• 英文别名: (R)-allyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-aminohexanoate；Fmoc-D-Lys-OAll；Fmoc-D-Lys-O-allyl；Allyl (((9H-fluoren-9-yl)methoxy)carbonyl)-D-lysinate；prop-2-enyl (2R)-6-amino-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoate
• 化学式: C₂₄H₂₈N₂O₄
• 分子量: 408.497
• InChiKey: KHXOBMIHCYCHQB-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-α-Fmoc-D-Lys allyl ester 在 N-甲基吗啉 、 苯硅烷 、 palladium diacetate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Coupling of Carbon and Peptide Nanotubes

  摘要：

  Two of the main types of nanotubular architectures are the single-walled carbon nanotubes (SWCNTs) and the self-assembling cyclic peptide nanotubes (SCPNs). We here report the preparation of the dual composite resulting from the ordered combination of both tubular motifs. In the resulting architecture, the SWCNTs can act as templates for the assembly of SCPNs that engage the carbon nanotubes noncovalently via pyrene "paddles", each member of the resulting hybrid stabilizing the other in aqueous solution. The particular hybrids obtained in the present study formed highly ordered oriented arrays and display complementary properties such as electrical conductivity. Furthermore, a self-sorting of the cyclic peptides toward semiconducting rather than metallic SWCNTs is also observed in the aqueous dispersions. It is envisaged that a broad range of exploitable properties may be achieved and/or controlled by varying the cyclic peptide components of similar SWCNT/SCPN hybrids.

  DOI：

  10.1021/ja410901r
• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-D-赖氨酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-α-Fmoc-D-Lys allyl ester
  参考文献：
  名称：

  通过氮丙啶醛二聚体驱动的三组分耦合固相平行合成功能化的中大型环状拟肽

  摘要：

  描述了使用氮丙啶醛二聚体驱动的三组分偶联的大环肽的首次固相平行合成。该方法支持合成9至18元含氮丙啶的大环，然后通过氮丙啶环的亲核开环将其官能化。这构成了快速并行合成大环肽的可靠方法。

  DOI：

  10.1002/chem.201500068

文献信息

• Systemic Antibacterial Activity of Novel Synthetic Cyclic Peptides
  作者：Véronique Dartois、Jorge Sanchez-Quesada、Edelmira Cabezas、Ellen Chi、Chad Dubbelde、Carrie Dunn、Juan Granja、Colleen Gritzen、Dana Weinberger、M. Reza Ghadiri、Thomas R. Parr

  DOI：10.1128/aac.49.8.3302-3310.2005

  日期：2005.8

  Cyclic peptides with an even number of alternatingd,l-α-amino acid residues are known to self-assemble into organic nanotubes. Such peptides previously have been shown to be stable upon protease treatment, membrane active, and bactericidal and to exert antimicrobial activity againstStaphylococcus aureusand other gram-positive bacteria. The present report describes the in vitro and in vivo pharmacology of selected members of this cyclic peptide family. The intravenous (i.v.) efficacy of six compounds with MICs of less than 12 μg/ml was tested in peritonitis and neutropenic-mouse thigh infection models. Four of the six peptides were efficacious in vivo, with 50% effective doses in the peritonitis model ranging between 4.0 and 6.7 mg/kg against methicillin-sensitiveS. aureus(MSSA). In the thigh infection model, the four peptides reduced the bacterial load 2.1 to 3.0 log units following administration of an 8-mg/kg i.v. dose. Activity against methicillin-resistantS. aureuswas similar to MSSA. The murine pharmacokinetic profile of each compound was determined following i.v. bolus injection. Interestingly, those compounds with poor efficacy in vivo displayed a significantly lower maximum concentration of the drug in serum and a higher volume of distribution at steady state than compounds with good therapeutic properties.S. aureuswas unable to easily develop spontaneous resistance upon prolonged exposure to the peptides at sublethal concentrations, in agreement with the proposed interaction with multiple components of the bacterial membrane canopy. Although additional structure-activity relationship studies are required to improve the therapeutic window of this class of antimicrobial peptides, our results suggest that these amphipathic cyclicd,l-α-peptides have potential for systemic administration and treatment of otherwise antibiotic-resistant infections.

  摘要已知具有偶数个交替的 d,l-α-氨基酸残基的环肽可以自组装成有机纳米管。以前的研究表明，这种肽在蛋白酶处理后具有稳定性、膜活性和杀菌性，并对金黄色葡萄球菌和其他革兰氏阳性细菌具有抗菌活性。本报告介绍了该环肽家族部分成员的体外和体内药理学。在腹膜炎和嗜中性粒细胞小鼠大腿感染模型中，对 MIC 小于 12 μg/ml 的六种化合物进行了静脉注射药效测试。在腹膜炎模型中，六种肽中的四种对甲氧西林敏感金黄色葡萄球菌（MSSA）的50%有效剂量为4.0至6.7毫克/千克。在大腿感染模型中，静脉注射 8 毫克/千克的剂量后，四种肽能使细菌量减少 2.1 至 3.0 log 单位。对耐甲氧西林金黄色葡萄球菌的活性与 MSSA 相似。在静脉注射后，测定了每种化合物的小鼠药代动力学特征。有趣的是，与疗效好的化合物相比，体内疗效差的化合物在血清中的最大药物浓度明显较低，稳态分布容积也较高。金黄色葡萄球菌在长期接触亚致死浓度的肽后不易产生自发抗药性，这与所提出的与细菌膜顶盖的多种成分相互作用是一致的。虽然还需要进行更多的结构-活性关系研究来改善这类抗菌肽的治疗窗口，但我们的研究结果表明，这些两性环d,l-α-肽具有全身给药和治疗抗生素耐药性感染的潜力。
• Antibacterial cyclic d,l-α-glycopeptides
  作者：Leila Motiei、Shai Rahimipour、Desiree A. Thayer、Chi-Huey Wong、M. Reza Ghadiri

  DOI：10.1039/b902455g

  日期：——

  We report the design, synthesis, membrane activity, biophysical characterization, and in vitro antibacterial activities of cationic cyclic D,L-α-glycopeptides bearing D-glucosamine (GlcNH2), D-galactose (Gal), or D-mannose (Man) glycosyl side chains.

  我们报告了带有D-氨基葡萄糖（GlcNH2）、D-半乳糖（Gal）或D-甘露糖（Man）糖苷侧链的阳离子环状D,L-α-糖肽的设计、合成、膜活性、生物物理特性及体外抗菌活性。
• A New Highly Versatile Handle for Chemistry on a Solid Support: The Pipecolic Linker
  作者：Nicolas Masurier、Paweł Zajdel、Pascal Verdié、Maciej Pawłowski、Muriel Amblard、Jean Martinez、Gilles Subra

  DOI：10.1002/chem.201201452

  日期：2012.9.10

  The versatility of the pipecolic linker (Pip‐linker) is illustrated by the synthesis of modified amino acids, C‐terminal‐modified pseudopeptides, and cyclic peptides, through side‐chain anchoring of a lysine residue (see figure). Introduction of the first residue was easily accomplished and the Pip‐linker revealed to be robust enough to support various chemical modifications.

  通过赖氨酸残基的侧链锚定，修饰氨基酸，C末端修饰的伪肽和环状肽的合成说明了管状连接子（Pip-linker）的多功能性。第一个残基的引入很容易完成，并且Pip-linker具有足够的鲁棒性以支持各种化学修饰。
• LYSINE-GLUTAMIC ACID DIPEPTIDE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150073173A1

  公开（公告）日：2015-03-12

  The invention relates to compounds of the formula to a process for making same and to the use of the products in the solid phase peptide synthesis. The compounds of formula I are versatile peptide intermediates for the solid phase peptide synthesis (SPPS) of peptide drugs which comprise a Glu-fatty alkyl side chain building block attached to a Lys-part of the peptide chain.

  本发明涉及如下公式的化合物，其制备方法以及将所得产物用于固相肽合成的用途。公式 I 的化合物是用于固相肽合成（SPPS）的多功能肽中间体，用于合成具有Glu-脂肪烷基侧链构建块的肽药物，该构建块连接到肽链的Lys部分。
• Solid-Phase Parallel Synthesis of Functionalised Medium-to-Large Cyclic Peptidomimetics through Three-Component Coupling Driven by Aziridine Aldehyde Dimers
  作者：Adam P. Treder、Jennifer L. Hickey、Marie-Claude J. Tremblay、Serge Zaretsky、Conor C. G. Scully、John Mancuso、Annie Doucet、Andrei K. Yudin、Eric Marsault

  DOI：10.1002/chem.201500068

  日期：2015.6.15

  solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.

  描述了使用氮丙啶醛二聚体驱动的三组分偶联的大环肽的首次固相平行合成。该方法支持合成9至18元含氮丙啶的大环，然后通过氮丙啶环的亲核开环将其官能化。这构成了快速并行合成大环肽的可靠方法。