n-Fmoc-a-methyl-DL-phenylalanine | 212394-94-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: n-Fmoc-a-methyl-DL-phenylalanine
• 英文别名: 2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methyl-3-phenylpropanoic acid
• CAS: 212394-94-0
• 化学式: C₂₅H₂₃NO₄
• 分子量: 401.462
• InChiKey: KLBKBAAOPOXFSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  n-Fmoc-a-methyl-DL-phenylalanine 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 (R or S)CαMePhe-Asp(OtBu)-Val-Val-Gly-NH2
  参考文献：
  名称：

  三角肌C的Phe3取代类似物。δ阿片受体识别肽中芳香环的空间构象和形貌。

  摘要：

  为了研究deltorphin C第3位氨基酸残基的电子，疏水和构象性质对与δ和μ阿片受体结合的贡献，一系列5和6元环和双环氨基酸取代通过溶液合成方法制备3位上的化合物。通常，取代对高δ亲和力（Ki delta）和δ选择性（Ki mu / Ki delta）有害。然而，认识到几个显着的例外：含有受约束的双环结构Aic3和（R或S）Atc3的肽增强了delta亲和力，但是只有后者相对于deltorphin C（= 661）才将delta选择性提高了4倍（= 2475）。在另一个极端，N alpha MePh3的δ亲和力下降了900倍。[N alpha MePhe3]-，[（R或S）C alpha MePhe3]-，[Tic3]-，[Aic3]-的生物测定 和[（R或S）Atc3] deltorphin C使用豚鼠回肠（GPI）和小鼠输精管（MVD）的mu和δ生物活性，分别揭示了MVD生物活性与

  DOI：

  10.1021/jm00076a001
• 作为产物：
  描述：

  alpha-甲基-DL-苯丙氨酸 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 phosphate buffer 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 n-Fmoc-a-methyl-DL-phenylalanine
  参考文献：
  名称：

  Novel Selective Inhibitors of the Interaction of Individual Nuclear Hormone Receptors with a Mutually Shared Steroid Receptor Coactivator 2

  摘要：

  Nuclear hormone receptor (NR) signaling, currently a therapeutic target in multiple diseases, involves an ordered series of protein interactions to regulate transcription in response to changing hormone levels. Later steps in the process of ligand-dependent signaling are driven by a highly conserved interaction between the NRs and the steroid receptor coactivators (SRCs) that is effected by a conserved interaction motif (L1XXL2L3), known as an NR box. Using computational design and combinatorial chemistry, we have produced novel alpha-helical proteomimetics of the second NR box of SRC2 that exploit structural differences between human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human thyroid hormone receptor beta (hTRbeta). The resulting library sequentially replaced each leucine with non-natural side chains. Screening this library using a quantitative competition assay revealed compounds that selectively inhibit the interaction of SRC2-2 with each individual NR in preference to its interaction with the other NR. This approach generated highly selective compounds from one that had no specificity for a particular family member. These compounds represent the first family-member-selective competitive inhibitors of the protein interactions of transcription factors.

  DOI：

  10.1021/ja0348391

文献信息

• Solution and solid phase combinatorial synthesis of peptidomimetic library containing diversified α-methylated amino acids
  作者：Sang Woong Kim、You Seung Shin、Seonggu Ro

  DOI：10.1016/s0960-894x(98)00279-0

  日期：1998.7

  A combinatorial peptidomimetic library containing diversified alpha-methylated amino acids was generated by the Ugi four component condensation (4cc) reaction from acids, amines, isocyanides and ketones in both solution and solid phase synthetic procedures. This one-pot methodology overall gave fair to good yields, which compare well with multi-step syntheses.

  在溶液和固相合成方法中，通过酸，胺，异氰酸酯和酮的Ugi四组分缩合（4cc）反应生成了包含多种α-甲基化氨基酸的组合拟肽文库。这种一锅法的方法总体上可以使良品率达到合理水平，与多步合成方法相比，它具有很高的优势。
• SYNTHETIC APOLIPOPROTEINS, AND RELATED COMPOSITIONS METHODS AND SYSTEMS FOR NANOLIPOPROTEIN PARTICLES FORMATION
  申请人：LAWRENCE LIVERMORE NATIONAL SECURITY, LLC

  公开号：US20180186860A1

  公开（公告）日：2018-07-05

  Synthetic apolipoproteins based on native/naturally occurring homolog proteins can be prepared using solid-phase peptide synthesis approaches combined with native chemical ligation methods to create analogs of full length apolipoproteins. The chemical synthesis is expected to allow introduction of non-natural amino acids, e.g., α,α′-dialkyl amino acids, with a periodicity that encourages both helix formation and amphipathicity. Such apolipoprotein analogs are expected to encourage, in some embodiments, facile and more complete NLP formation, enabling consideration of full spectrum of nanoparticle-based biotechnology applications ranging from therapeutic sequestration and delivery to energy/biofuel production to biopolymer production.
• [EN] NOVEL SHORT-CHAIN PEPTIDES AS KAPPA (κ) OPIOID RECEPTORS (KOR) AGONIST<br/>[FR] NOUVEAUX PEPTIDES À CHAÎNE COURTE EN TANT QU'AGONISTES DES RÉCEPTEURS OPIOÏDES KAPPA (Κ) (KOR)
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2016181408A2

  公开（公告）日：2016-11-17

  The present invention relates to novel short-chain peptides of the general formula (I), which are selective and peripherally acting KOR agonist, their tautomeric forms, their enantiomers, their diastereoisomers, their stereoisomers, their pharmaceutically accepted salts, or prodrugs thereof which are useful in the treatment or prevention of diseases in which the Kappa (κ) opioid receptors (KOR) are involved, such as treatment or prevention of visceral pain, hyperalgesia, rheumatoid arthritic inflammation, osteoarthritic inflammation, IBD inflammation, IBS inflammation, ocular inflammation, otitic inflammation or autoimmune inflammation. The invention also relates to process for the manufacture of said short-chain peptides, and pharmaceutical compositions containing them and their use.