L-lysyl-L-lysine dihydrochloride

• 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
• 英文名称: L-lysyl-L-lysine dihydrochloride
• 英文别名: H-Lys-Lys-OH hydrochloride；(2S)-6-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]hexanoic acid;hydrochloride
• 化学式: C₁₂H₂₆N₄O₃*2ClH
• 分子量: 347.285
• InChiKey: ROGKVZGKYWMMAT-IYPAPVHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  145
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-lysyl-L-lysine dihydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 benzyl 6-{(S)-6-amino-2-[(S)-2,6-diaminohexanamido]hexanamido}hexanoate
  参考文献：
  名称：

  [EN] GLUCOSE-RESPONSIVE INSULIN CONJUGATES
  [FR] CONJUGUÉS D'INSULINE SENSIBLES AU GLUCOSE

  摘要：

  提供含有一个或多个线性寡聚糖团簇的葡萄糖响应胰岛素共轭物。这种胰岛素共轭物可能表现出对体内葡萄糖或α-甲基甘露糖等糖类的系统浓度响应的药代动力学（PK）和/或药效动力学（PD）特性，即使在向需要的受试者施用时，也无需外源多价糖结合分子。

  公开号：

  WO2020247297A1

文献信息

• Methods for delivery of nucleic acids
  申请人：Satishchandran C.

  公开号：US20060084617A1

  公开（公告）日：2006-04-20

  This invention features methods and compositions for delivery of nucleic acids (e.g., DNA, RNA, PNA, and hybrids thereof) to cells. The nucleic acid delivery complexes of the invention permit biologically active nucleic acids to be delivered to cells and organisms in vitro and in vivo in a manner and form that allows the nucleic acids to carry out their desired biological function.

  这项发明涉及用于将核酸（例如，DNA、RNA、PNA及其杂合体）递送到细胞中的方法和组合物。本发明的核酸递送复合物使得生物活性的核酸能够以某种方式和形式递送到体外和体内的细胞和生物体中，从而允许核酸执行其所需的生物学功能。
• [EN] CONJUGATE BASED SYSTEMS FOR CONTROLLED INSULIN DELIVERY<br/>[FR] SYSTÈMES À BASE DE CONJUGUÉS POUR L'ADMINISTRATION CONTRÔLÉE D'INSULINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2019125878A1

  公开（公告）日：2019-06-27

  The present disclosure provides conjugates that comprise an insulin molecule conjugated via a conjugate framework to two or more separate ligands that each include a saccharide, wherein the framework, ligand, saccharide and insulin molecule optionally comprise a fatty chain (e.g., a C8-30 fatty chain), wherein when said insulin molecule is conjugated both to a C8-30 fatty chain and one or more separate ligands that each include a saccharide, said C8-30 fatty chain is linked to insulin molecule only, and wherein when the framework or ligand comprises a fatty chain the insulin molecule is conjugated to two or more separate ligands. In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

  本公开提供了包含胰岛素分子通过一个共轭框架与两个或更多个单独的配体结合的共轭物，每个配体都包括一个糖苷的共轭物，其中该框架、配体、糖苷和胰岛素分子可选择包括一个脂肪链（例如，一个C8-30脂肪链），当所述胰岛素分子既与一个C8-30脂肪链结合又与一个或多个包括糖苷的单独的配体结合时，所述C8-30脂肪链仅与胰岛素分子连接，当该框架或配体包括一个脂肪链时，胰岛素分子与两个或更多个单独的配体结合。在某些实施例中，一个共轭物的特征在于，当将该共轭物注射给哺乳动物时，该共轭物的至少一个药代动力学（PK）和/或药效动力学（PD）特性对第二糖苷的血清浓度敏感。在某些实施例中，一个共轭物还具有持续的PK特性。除了使用和制备方法外，还提供了示例共轭物和缓释制剂。
• Synthesis of Peptide-Based Cyclophane Oligomers Having Multivalently Enhanced Guest-Binding Affinity
  作者：Osamu Hayashida、Tomomi Nakashima

  DOI：10.1246/bcsj.20120076

  日期：2012.6.15

  Water-soluble cyclophane dimer, trimer, tetramer, and pentamer were prepared by aminolysis of succinimidyl ester derivative of tetraaza[6.1.6.1]paracyclophane with lysine and the corresponding lysine peptide as a scaffold, followed by removal of the protecting groups. The present cyclophane oligomers showed enhanced guest-binding affinities toward fluorescent guests such as 6-p-toluidinonaphthalene-2-sulfonate, in comparison with those of monocyclic cyclophane, reflecting multivalency effects in macrocycles. The effects of multivalent macrocycles on the guest-binding of the present cyclophane oligomers were also confirmed by surface plasmon resonance (SPR) measurements.

  通过用赖氨酸和相应的赖氨酸肽作为支架，对四氮杂[6.1.6.1]对环芳烷的琥珀酰亚胺酯衍生物进行胺解反应，随后去除保护基团，制备了水溶性环芳烷二聚体、三聚体、四聚体和五聚体。与单环环芳烷相比，这些环芳烷寡聚体对6-对甲苯氨基萘-2-磺酸盐等荧光客体显示出增强的客体结合亲和力，反映了大环中的多价效应。通过表面等离子体共振（SPR）测量，也证实了多价大环对这些环芳烷寡聚体的客体结合的影响。
• Formation of Pyrazines in Maillard Model Systems of Lysine-Containing Dipeptides
  作者：Fien Van Lancker、An Adams、Norbert De Kimpe

  DOI：10.1021/jf903898t

  日期：2010.2.24

  respectively. Generally, the pyrazines were produced more in the case of dipeptides as compared to free amino acids. For reactions with glucose and methylglyoxal, this difference was mainly caused by the large amounts of 2,5(6)-dimethylpyrazine and trimethylpyrazine produced from the reactions with dipeptides. For reactions with glyoxal, the difference in pyrazine production was rather small and mostly unsubstituted

  尽管有关美拉德反应的大多数研究都集中在游离氨基酸上，但是关于肽和蛋白质对食品化学中这一重要反应的影响的信息很少。因此，研究了葡萄糖，甲基乙二醛或乙二醛与八种二肽与赖氨酸在N端的模型反应的形成，并与相应的游离氨基酸进行了对比，方法是通过搅拌棒吸附萃取（SBSE），然后是GC-MS分析。包含葡萄糖，甲基乙二醛和乙二醛的二肽的反应混合物分别产生27种，18种和2种不同的吡嗪。通常，与二肽相比，与游离氨基酸相比，吡嗪的产生更多。对于与葡萄糖和甲基乙二醛的反应，这种差异主要是由于与二肽反应产生的大量2,5（6）-二甲基吡嗪和三甲基吡嗪引起的。对于与乙二醛的反应，吡嗪生产的差异很小，并且形成了大部分未取代的吡嗪。提出并评价了由二肽形成吡嗪的反应机理。这项研究清楚地说明了肽产生风味化合物的能力，这种风味化合物可能不同于通过与游离氨基酸进行相应反应而获得的风味化合物。
• Cell-specific glycopeptide ligands
  申请人：Merck & Co., Inc.

  公开号：US04386026A1

  公开（公告）日：1983-05-31

  Cell-specific ligands comprising conjugates of saccharides and amino acids or peptides are synthesized from amino acids such as ornithine, lysine, peptides such as dilysine, diornithine or oligolysine and selected saccharides having reactive functional groups protected by appropriate blocking groups. Such glycopeptides are useful as tissue specific substances, which when coupled with bioactive materials through metabolizable or hydrolyzable linkages, deliver such bioactive materials to the selected site. In this manner, antiinflammatory drugs such as dexamethasone are linked through a metabolizable or hydrolyzable linkage and on administration to an animal suffering from inflammatory disease carries the drug to the site of inflammation for intracellular release. Other examples include the macrophage ligand N.sup.2 -N.sup.2, N.sup.6 -Bis-[3-(.alpha.-D-mannopyranosylthio)propionyl]-6-lysyl-N.sup.6 -[3-(.alpha.-D-mannopyranosylthio)propionyl]-L-lysine, 5, which when coupled to .beta.-glucocerebrosidase, can deliver the enzyme selectively to kupffer cells. This is useful in the enzyme replacement therapy of Gaucher's disease.

  由氨基酸（如鸟氨酸、赖氨酸）、肽（如二赖氨酸、二鸟氨酸或寡赖氨酸）和选定的具有适当阻断基保护的反应性官能团的糖组成的细胞特异性配体，可合成成糖肽。这些糖肽可作为组织特异性物质，通过可代谢或可水解的连接与生物活性材料结合，将这些生物活性材料传递到选择的部位。通过这种方式，如地塞米松等抗炎药物可通过可代谢或可水解的连接结合，并在给患有炎症性疾病的动物施用后将药物携带到炎症部位进行细胞内释放。其他例子包括巨噬细胞配体N.sup.2-N.sup.2，N.sup.6-Bis-[3-(.alpha.-D-甘露糖硫基)丙酰基]-6-赖氨酸-N.sup.6-[3-(.alpha.-D-甘露糖硫基)丙酰基]-L-赖氨酸，5，当它与β-葡糖苷酶结合时，可将酶有选择地传递到库普弗细胞。这对于高氏病的酶替代疗法非常有用。