(1R,2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentanecarboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (1R,2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentanecarboxylic acid
• 英文别名: (1S,2R)-Fmoc-2-amino-1-cyclopentanecarboxylic acid；cis-2-(9-Fluorenylmethoxycarbonylamino)cyclopentanecarboxylic acid；(1R,2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)cyclopentane-1-carboxylic acid
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: KTLDVIJVCPIJCM-MJGOQNOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  三氟乙酸五氟苯酯 、 (1R,2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentanecarboxylic acid 在 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 0.25h， 生成
  参考文献：
  名称：

  新型带有β-氨基酸间隔基的吡咯烷基PNA的合成与性能

  摘要：

  新型吡咯烷基肽核酸，其包含核碱基修饰的d-脯氨酸和β-氨基酸间隔基的交替序列，所述间隔基选自1-氨基吡咯烷-2-羧酸，d-氨基吡咯烷-2-羧酸，（1 R，2 S）-2固相法合成了α-氨基环戊烷羧酸和β-丙氨酸。凝胶结合位移试验表明，只有带有d-氨基吡咯烷-2-羧酸间隔基的高胸腺嘧啶PNA十聚体与（dA）10结合。

  DOI：

  10.1016/s0040-4039(01)01020-6
• 作为产物：
  描述：

  cis-2-aza-3-oxobicyclo<3.2.0>heptane 在 水 、 potassium hydrogencarbonate 作用下， 以 异丙醚 、 水 、 丙酮 为溶剂， 反应 288.0h， 生成 (1R,2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentanecarboxylic acid
  参考文献：
  名称：

  Hairpin Folding Behavior of Mixed α/β-Peptides in Aqueous Solution

  摘要：

  The invention of new strategies for the design of protein-mimetic oligomers that manifest the folding encoded in natural amino acid sequences is a significant challenge. In contrast to the a-helix, mimicry of protein beta-sheets is less understood. We report here the aqueous folding behavior of a prototype alpha-peptide hairpin model sequence varied at cross-strand positions by incorporation of 16 different beta-amino acid monomers. Our results provide a folding propensity scale for beta-residues in a protein beta-sheet context as well as high-resolution structures of several mixed-backbone alpha/beta-peptide hairpins in water.

  DOI：

  10.1021/ja2002346

文献信息

• Controlling the Helix Handedness of ααβ-Peptide Foldamers through Sequence Shifting
  作者：Monika Szefczyk、Ewelina Węglarz-Tomczak、Paulina Fortuna、Agnieszka Krzysztoń、Ewa Rudzińska-Szostak、Łukasz Berlicki

  DOI：10.1002/anie.201610154

  日期：2017.2.13

  Peptide foldamers containing both cis‐β‐aminocyclopentanecarboxylic acid and α‐amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ‐Peptides were found to fold into an unprecedented and well‐defined 16/17/15/18/14/17‐helix. By extending the length of the sequence or shifting a fragment

  使用CD和NMR光谱法筛选了包含顺式-β-氨基环戊烷羧酸和α-氨基酸残基的肽折叠剂，这些残基以各种序列模式（ααβ，αααβ，αβααβ和ααβαααβ）结合在一起，以形成螺旋的趋势。发现ααβ肽折叠成史无前例且定义明确的16/17/15/18/14 / 17-螺旋。通过延长序列的长度或将序列的片段从一个ααβ肽的一个末端移动到另一个末端，可以控制溶液中存在的左手和右手螺旋种群之间的平衡。肽序列的工程改造可能会导致化合物对选定的螺旋有义性有强烈的倾向，或者对相反有义的螺旋构象有很强的混合性。
• Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity
  作者：Andreas M. Voll、Christian Meyners、Martha C. Taubert、Thomas Bajaj、Tim Heymann、Stephanie Merz、Anna Charalampidou、Jürgen Kolos、Patrick L. Purder、Thomas M. Geiger、Pablo Wessig、Nils C. Gassen、Andreas Bracher、Felix Hausch

  DOI：10.1002/anie.202017352

  日期：2021.6.7

  Subtype selectivity represents a challenge in many drug discovery campaigns. A typical example is the FK506 binding protein 51 (FKBP51), which has emerged as an attractive drug target. The most advanced FKBP51 ligands of the SAFit class are highly selective vs. FKBP52 but poorly discriminate against the homologs and off-targets FKBP12 and FKBP12.6. During a macrocyclization pilot study, we observed

  亚型选择性是许多药物发现活动中的一个挑战。一个典型的例子是 FK506 结合蛋白 51 (FKBP51)，它已成为一个有吸引力的药物靶点。SAFit 类最先进的 FKBP51 配体相对于 FKBP52 具有高度选择性，但对同系物和脱靶 FKBP12 和 FKBP12.6 的区分能力较差。在一项大环化试点研究中，我们观察到许多大环类似物对 FKBP51 的偏好超出了 FKBP12 和 FKBP12.6 的范围。结构研究表明，这些大环化合物以一种具有瞬时构象的新结合模式结合，这对于小 FKBP 来说是不利的。使用构象敏感测定，我们证明这种结合模式发生在溶液中，并且是此类新型化合物的特征。发现的大环化合物是非免疫抑制性的，与细胞中的 FKBP51 结合，并阻断 FKBP51 对 IKKα 的细胞作用。我们的研究结果为改进的 FKBP51 配体提供了新的化学支架，并为增强选择性提供了结构基础。
• [EN] NOVEL ARYL-CYANOGUANIDINE COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS D'ARYL-CYANOGUANIDINE
  申请人：BAYER PHARMA AG

  公开号：WO2016166186A1

  公开（公告）日：2016-10-20

  The present invention relates to protein-lysine N-methyltransferase SMYD2 (SET and MYND domain-containing protein 2) inhibitors, in particular SMYD2-inhibitory substituted cyanoguanidine- pyrazolines of general formula (I), wherein R1, R2, R3, R4 and R5 have the meaning as described and defined herein, as well as to pharmaceutical compositions comprising compounds according to the invention and to their prophylactic and therapeutic use for hyperproliferative disorders, in particular for cancer, respectively tumour disorders. The present invention furthermore relates to the use of SMYD2 inhibitors for benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, neurodegenerative disorders, inflammatory disorders, atherosclerotic disorders and the control of male fertility.

  本发明涉及蛋白酰赖氨酸N-甲基转移酶SMYD2（SET和MYND结构域含有蛋白2）抑制剂，特别是通式（I）的SMYD2抑制剂取代氰基胍-吡唑啉，其中R1，R2，R3，R4和R5具有如下所述和定义的含义，以及包含根据本发明的化合物的制药组合物以及它们在高增殖性疾病，特别是癌症，以及肿瘤性疾病的预防和治疗中的预防和治疗用途。本发明还涉及SMYD2抑制剂用于良性增生，动脉粥样硬化性疾病，败血症，自身免疫性疾病，血管疾病，病毒感染，神经退行性疾病，炎症性疾病，动脉粥样硬化性疾病和男性生育控制。
• Human testis expressed patched like protein
  申请人：Aeomica, Inc.

  公开号：EP1229046A2

  公开（公告）日：2002-08-07

  The invention provides isolated nucleic acids that encode HTPL, including two isoforms, and fragments thereof, vectors for propagating and expressing HTPL nucleic acids, host cells comprising the nucleic acids and vectors of the present invention, proteins, protein fragments, and protein fusions of the novel HTPL isoforms, and antibodies thereto. The invention further provides transgenic cells and non-human organisms comprising human HTPL nucleic acids, and transgenic cells and non-human organisms with targeted disruption of the endogenous orthologue of the human HTPL gene. The invention further provides pharmaceutical formulations of the nucleic acids, proteins, and antibodies of the present invention, and diagnostic, investigational, and therapeutic methods based on the HTPL nucleic acids, proteins, and antibodies of the present invention.

  本发明提供了编码 HTPL（包括两种异构体）的分离核酸及其片段、繁殖和表达 HTPL 核酸的载体、包含本发明核酸和载体的宿主细胞、新型 HTPL 异构体的蛋白质、蛋白质片段和蛋白质融合体及其抗体。本发明进一步提供了包含人类 HTPL 核酸的转基因细胞和非人类生物体，以及靶向干扰人类 HTPL 基因内源直向同源物的转基因细胞和非人类生物体。本发明进一步提供了本发明核酸、蛋白质和抗体的药物制剂，以及基于本发明 HTPL 核酸、蛋白质和抗体的诊断、研究和治疗方法。
• A human protein kinase domain-containing protein
  申请人：Aeomica, Inc.

  公开号：EP1227156A2

  公开（公告）日：2002-07-31

  The invention provides isolated nucleic acids that encode a human protein kinase domain-containing portein (STTK), and fragments thereof, vectors for propagating and expressing STTK nucleic acids, host cells comprising the nucleic acids and vectors of the present invention, proteins, protein fragments, and protein fusions of the novel STTK isoforms, and antibodies thereto. The invention further provides transgenic cells and non-human organisms comprising STTK nucleic acids, and transgenic cells and non-human organisms with targeted disruption of the endogenous orthologue of the STTK gene. The invention further provides pharmaceutical formulations of the nucleic acids, proteins, and antibodies of the present invention, and diagnostic, investigational, and therapeutic methods based on the STTK nucleic acids, proteins, and antibodies of the present invention.

  本发明提供了编码含人蛋白激酶结构域的门冬氨酸（STTK）的分离核酸及其片段、用于繁殖和表达STTK核酸的载体、包含本发明核酸和载体的宿主细胞、新型STTK异构体的蛋白质、蛋白质片段和蛋白质融合体及其抗体。本发明进一步提供了包含 STTK 核酸的转基因细胞和非人类生物体，以及定向破坏 STTK 基因内源直向同源物的转基因细胞和非人类生物体。本发明进一步提供了本发明核酸、蛋白质和抗体的药物制剂，以及基于本发明 STTK 核酸、蛋白质和抗体的诊断、研究和治疗方法。