7-赖氨酰丙氨酰-4-甲基香豆素酰胺 | 94149-28-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 7-赖氨酰丙氨酰-4-甲基香豆素酰胺
• 英文名称: Lys-Ala-AMC
• 英文别名: Lys-Ala-7-amido-4-methylcoumarin；lysylalanylaminomethylcoumarin；Lys-Ala-MCA；LysAlaAcm；KA-AMC；KA-MCA；L-Alaninamide, L-lysyl-N-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)-；(2S)-2,6-diamino-N-[(2S)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopropan-2-yl]hexanamide
• CAS: 94149-28-7
• 化学式: C₁₉H₂₆N₄O₄
• 分子量: 374.44
• InChiKey: BEIXTDYXKGFYLC-WFASDCNBSA-N

物化性质

• 沸点：
  701.6±60.0 °C(Predicted)
• 密度：
  1.257±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-赖氨酰丙氨酰-4-甲基香豆素酰胺 在 乙二胺四乙酸 、 dipeptydyl-peptidase DPP₅ 、 sodium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.5h， 生成 (S)-2-((S)-2,6-Diamino-hexanoylamino)-propionic acid
  参考文献：
  名称：

  Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

  摘要：

  Background: Dipeptidyl-peptidases (DPPs) are key factors for amino acid metabolism and bacterial growth of asaccharolytic Porphyromonas gingivalis. Results: DPP5, which is specific for Ala and hydrophobic residues, is expressed in the periplasmic space of P. gingivalis.Conclusion: DPP5 was discovered in prokaryotes for the first time. Significance: The discovery of DPP5 expands understanding of amino acid and energy metabolism in prokaryotes. Porphyromonas gingivalis, a Gram-negative asaccharolytic anaerobe, is a major causative organism of chronic periodontitis. Because the bacterium utilizes amino acids as energy and carbon sources and incorporates them mainly as dipeptides, a wide variety of dipeptide production processes mediated by dipeptidyl-peptidases (DPPs) should be beneficial for the organism. In the present study, we identified the fourth P. gingivalis enzyme, DPP5. In a dpp4-7-11-disrupted P. gingivalis ATCC 33277, a DPP7-like activity still remained. PGN_0756 possessed an activity indistinguishable from that of the mutant, and was identified as a bacterial orthologue of fungal DPP5, because of its substrate specificity and 28.5% amino acid sequence identity with an Aspergillus fumigatus entity. P. gingivalis DPP5 was composed of 684 amino acids with a molecular mass of 77,453, and existed as a dimer while migrating at 66 kDa on SDS-PAGE. It preferred Ala and hydrophobic residues, had no activity toward Pro at the P1 position, and no preference for hydrophobic P2 residues, showed an optimal pH of 6.7 in the presence of NaCl, demonstrated K-m and k(cat)/K-m values for Lys-Ala-MCA of 688 m and 11.02 m(-1) s(-1), respectively, and was localized in the periplasm. DPP5 elaborately complemented DPP7 in liberation of dipeptides with hydrophobic P1 residues. Examinations of DPP- and gingipain gene-disrupted mutants indicated that DPP4, DPP5, DPP7, and DPP11 together with Arg- and Lys-gingipains cooperatively liberate most dipeptides from nutrient oligopeptides. This is the first study to report that DPP5 is expressed not only in eukaryotes, but also widely distributed in bacteria and archaea.

  DOI：

  10.1074/jbc.m113.527333
• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[[(2S)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopropan-2-yl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxohexan-2-yl]carbamate 生成 7-赖氨酰丙氨酰-4-甲基香豆素酰胺
  参考文献：
  名称：

  SAKAKIBARA, SYUNNEHJ

  摘要：

  DOI：

文献信息

• [EN] NA-ACYL DERIVATIVES OF AMINOACYL-2-CYANOPYRROLIDINE-INHIBITORS OF PROLYL ENDOPEPTIDASE AND DIPEPTIDYL PEPTIDASE-IV, HAVING HYPOGLYCEMIC, ANTIHYPOXIC, NEUROPROTECTIVE ACTION AND ACTION OF COGNITIVE FUNCTION IMPROVEMENT<br/>[FR] DÉRIVÉS NA-ACYLE D'AMINOACYL-2-CYANOPYRROLIDINE INHIBANT LA PROLYL ENDOPEPTIDASE ET LA DIPEPTIDYL PEPTIDASE-IV, PRÉSENTANT UNE ACTION HYPOGLYCÉMIQUE, ANTIHYPOXIQUE ET NEUROPROTECTRICE ET AMÉLIORANT LES FONCTIONS COGNITIVES
  申请人：DAPHOT ENTERPRAISES LTD

  公开号：WO2014054980A1

  公开（公告）日：2014-04-10

  The subject of the present invention is nα-acyl derivatives of aminoacyl-2-cyanopyrrolidine - inhibitors of prolyl endopeptidase and dipeptidyl peptidase-iv, having hypoglycemic, antihypoxic, neuroprotective action and action of cognitive function improvement.

  本发明的主题是氨酰基-2-氰基吡咯烷的nα-酰基衍生物 - 脯氨酸内切肽酶和二肽基肽酶-IV的抑制剂，具有降糖、抗缺氧、神经保护作用和改善认知功能的作用。
• Methods of modifying N-termini of a peptide or protein using transferases
  申请人：The Trustees of the University of Pennsylvania

  公开号：US09376700B2

  公开（公告）日：2016-06-28

  The invention includes a selective method of modifying the N-terminus of a protein using an aminoacyl tRNA transferase. In certain embodiments, the method comprises contacting a solution of the protein or peptide with a transferase and a derivative of a molecule, whereby the N-terminus of the protein or peptide is derivatized with the molecule.

  该发明涉及使用氨酰基tRNA转移酶选择性地修改蛋白质的N-末端的方法。在某些实施例中，该方法包括将蛋白质或肽溶液与转移酶和分子衍生物接触，从而使蛋白质或肽的N-末端与该分子衍生物发生衍生化反应。
• Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins
  作者：Yanxin J. Wang、D. Miklos Szantai-Kis、E. James Petersson

  DOI：10.1039/c6ob01020b

  日期：——

  that thioamides can be incorporated into proteins by native chemical ligation (NCL) with Cys as a ligation handle. In this study, we report the expansion of this strategy into non-Cys ligation sites, utilizing radical initiated desulfurization to “erase” the side chain thiol after ligation. The reaction exhibited high chemoselectivity against thioamides, which can be further enhanced with thioacetamide

  硫酰胺是规范酰胺键的单原子取代，并已被证明是蛋白质折叠研究中用途广泛且干扰最小的探针。先前，我们的小组表明，可以通过以Cys作为连接柄的天然化学连接（NCL）将硫酰胺掺入蛋白质中。在这项研究中，我们报告了该策略扩展到非Cys的连接位点，利用自由基引发的脱硫作用在连接后“擦除”侧链硫醇。该反应表现出对硫代酰胺的高化学选择性，可以用硫代乙酰胺作为牺牲清除剂进一步提高其选择性。作为概念验证的例子，我们证明了将硫酰胺探针掺入56个氨基酸的蛋白质（蛋白质G的B1结构域（GB1））中。最后，
• Expressed Protein Ligation at Methionine: N-Terminal Attachment of Homocysteine, Ligation, and Masking
  作者：Tomohiro Tanaka、Anne M. Wagner、John B. Warner、Yanxin J. Wang、E. James Petersson

  DOI：10.1002/anie.201302065

  日期：2013.6.10

  A useful handle: One major limitation of protein semi‐synthesis is the need for Cys at the ligation site in native chemical ligation reactions. It is shown that a transferase enzyme can deliver homocysteine to the N‐terminus of an expressed protein (see scheme). Homocysteine can be used in a ligation reaction and then converted to Met. This allows one to use the MetArg or MetLys motif as a point of

  一个有用的句柄：蛋白质半合成的一个主要限制是在天然化学连接反应中需要在连接位点使用 Cys。结果表明，转移酶可以将同型半胱氨酸传递到表达蛋白质的 N 端（参见方案）。同型半胱氨酸可用于连接反应，然后转化为 Met。这允许人们使用 MetArg 或 MetLys 基序作为半合成中的断开点。
• Mutations of key substrate binding residues of leishmanial peptidase T alter its functional and structural dynamics
  作者：Saleem Yousuf Bhat、Insaf Ahmed Qureshi

  DOI：10.1016/j.bbagen.2019.129465

  日期：2020.1

  carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently, while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364

  背景 M20氨基肽酶（例如肽酶T（PepT））在蛋白质降解途径的最终阶段涉及寡肽的水解，以维持营业额。因此，对PepT的特异性抑制作用对于新型下一代抗真菌药的开发很有效。这项工作描述了金属依赖性，底物偏好和对PepT的抑制，并详细证明了其两个保守的底物结合残基的作用。 方法 使用肽底物和拟肽抑制剂的方案纯化和鉴定PepT。用一系列生化，生物物理和结构生物学方法对残基T364和N378进行突变和表征。 结果 PepT序列带有M20肽酶典型的保守基序，我们的生物化学工作表明，这种胞质酶具有广泛的底物特异性，对在P 1位置带有丙氨酸的肽具有最佳的切割偏好。拟肽类阿马他汀和肌动蛋白通过与底物竞争结合到活性位点而占据了S 1口袋，并有效抑制了PepT，而香菜碱A和Bestatin的抑制作用较差。我们进一步表明，保守的底物结合残基（T364和N378）向丙氨酸的突变影响了结构，降低了底物结合并改变了这种二聚酶的酰胺分解活性。