果糖基-赖氨酸 | 21291-40-7

• 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: 果糖基-赖氨酸
• 中文别名: 3-(4-氯乙基-苯基)-丙酸乙基酯
• 英文名称: fructoselysine
• 英文别名: Fructosyl-lysine；(2S)-2-amino-6-[[(3S,4R,5R)-3,4,5,6-tetrahydroxy-2-oxohexyl]amino]hexanoic acid
• CAS: 21291-40-7
• 化学式: C₁₂H₂₄N₂O₇
• 分子量: 308.332
• InChiKey: BFSYFTQDGRDJNV-AYHFEMFVSA-N

物化性质

• 熔点：
  >120°C (dec.)
• 沸点：
  654.5±55.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于甲醇（轻微加热）、水（轻微超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  21
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  173
• 氢给体数：
  7
• 氢受体数：
  9

制备方法与用途

生物活性

Fructosyl-lysine（果糖赖氨酸）是葡萄糖与赖氨酸通过美拉德反应生成的一种氨基糖基化产物。它作为葡萄糖烷的前体，葡萄糖烷是一种赖氨酸-精氨酸蛋白交联物，在糖尿病检测中具有重要意义。

靶点

IC50: 前体至葡萄糖pane

体外研究

Fructosyl-lysine（5 mM；0.5小时）催化ATP依赖性的[14C]果糖赖氨酸转化为阴离子产物，表明在大肠杆菌提取物中存在果糖赖氨酸激酶活性。Fructosyl-lysine（100 μM；1小时）含有碳水化合物成分，并显示出被磷酸化的能力，在大肠杆菌提取物中可以被转换为葡萄糖6-磷酸。Fructosyl-lysine（25 mM；25小时）使大肠杆菌以大约三分之一的速率生长，而赖氨酸本身在没有其他碳源的情况下不支持生长，也不影响以葡萄糖作为碳源时的大肠杆菌生长。

体内研究

在糖尿病大鼠中，果糖赖氨酸和AGE残基显著增加，主要出现在肾小球、视网膜、坐骨神经及血浆蛋白中。

反应信息

• 作为反应物：
  描述：

  果糖基-赖氨酸 在 盐酸 作用下， 以 水 为溶剂， 反应 4.0h， 生成 N6-[2-(2-呋喃基)-2-氧代乙基]-L-赖氨酸
  参考文献：
  名称：

  Glucoselysine is derived from fructose and accumulates in the eye lens of diabetic rats

  摘要：

  Prolonged hyperglycemia generates advanced glycation end-products (AGEs), which are believed to be involved in the pathogenesis of diabetic complications. In the present study, we developed a polyclonal antibody against fructose-modified proteins (Fru-P antibody) and identified its epitope as glucoselysine (GL) by NMR and LC-electrospray ionization (ESI)-quadrupole TOF (QTOF) analyses and evaluated its potential role in diabetes sequelae. Although the molecular weight of GL was identical to that of fructoselysine (FL), GL was distinguishable from FL because GL was resistant to acid hydrolysis, which converted all of the FLs to furosine. We also detected GL in vitro when reduced BSA was incubated with fructose for 1 day. However, when we incubated reduced BSA with glucose, galactose, or mannose for 14 days, we did not detect GL, suggesting that GL is dominantly generated from fructose. LC-ESI-MS/MS experiments with synthesized [C-13(6)]GL indicated that the GL levels in the rat eye lens time-dependently increase after streptozotocin-induced diabetes. We observed a 31.3-fold increase in GL 8 weeks after the induction compared with nondiabetic rats, and N epsilon-(carboxymethyl)lysine and furosine increased by 1.7- and 21.5-fold, respectively, under the same condition. In contrast, sorbitol in the lens levelled off at 2 weeks after diabetes induction. We conclude that GL may be a useful biological marker to monitor and elucidate the mechanism of protein degeneration during progression of diabetes.

  DOI：

  10.1074/jbc.ra119.010744
• 作为产物：
  描述：

  L-赖氨酸 、 葡萄糖 以 甲醇 为溶剂， 反应 4.0h， 生成 果糖基-赖氨酸
  参考文献：
  名称：

  리시닐-프럭토오즈(Lysinyl-Fructose, LF)를 포함하는 혈당상승 억제제 및 그 제조방법

  摘要：

  本发明涉及一种制备Lysinyl-Fructose（LF）的方法，以及由该方法制备的LF对大鼠肠道α-葡萄糖苷酶、猪胰脏α-淀粉酶、大鼠肠道蔗糖酶、大鼠肠道麦芽糖酶、大鼠肠道葡萄糖淀粉酶的体外抑制活性以及对淀粉和蔗糖在体内分解的体内抑制活性进行了研究。根据这些结果，通过上述方法制备的LF可用于预防糖尿病、治疗糖尿病以及预防糖尿病并发症。

  公开号：

  KR20190004515A

文献信息

• Compounds and methods for therapeutic intervention in preventing diabetic complications and procedures for assessing a diabetic's risk of developing complications and determining the efficacy of therapeutic intervention
  申请人：——

  公开号：US20020111291A1

  公开（公告）日：2002-08-15

  Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins), which are believed to be a contributing cause of diabetic complications. Also disclosed are therapeutic methods of using such inhibitors to reduce formation of AGE-proteins and thereby lessen, reduce and delay diabetic complications and the effects of glycogen storage diseases, including Fanconi's syndrome. Methods for assessing a diabetic's risk of developing complications and for determining the efficacy of the disclosed inhibitor therapy by measuring the ratio of 3DG to 3DF in a biological sample following an oral dose of a fructose-lysine-containing food product are also disclosed.

  本文披露了一类化合物，可以抑制酶催化将果糖赖氨酸转化为果糖赖氨酸-3-磷酸酯的反应，这是一种新发现的代谢途径中依赖ATP的反应。根据该途径的正常功能，果糖赖氨酸-3-磷酸酯（FL3P）被分解为游离赖氨酸、无机磷酸盐和3-脱氧葡萄糖酮（3DG），后者是一种具有反应性的蛋白质修饰剂。3DG可以通过还原为3-脱氧果糖（3DF）来解毒，也可以与内源蛋白质反应形成高级糖基化终产物修饰的蛋白质（AGE-蛋白），据信这是糖尿病并发症的一个促发因素。此外，还披露了使用这种抑制剂的治疗方法，以减少AGE-蛋白的形成，从而减轻、减少和延迟糖尿病并发症和糖原贮积病（包括范科尼综合征）的影响。还披露了通过在口服含果糖赖氨酸的食品后测量生物样品中3DG与3DF比值来评估糖尿病患者发生并发症的风险和确定披露的抑制剂疗法的疗效的方法。
• Fructoseamine 3 kinase and the formation of collagen and elastin
  申请人：Tobia Annette

  公开号：US20070065443A1

  公开（公告）日：2007-03-22

  The invention relates to the discovery that levels of collagen and elastin can be modulated by changing the flux through the Amadori Pathway and that copper containing compounds and complexes inhibit the enzyme fructoseamine-3-kinase.

  本发明涉及到一项发现，即通过改变Amadori途径的通量可以调节胶原蛋白和弹性蛋白的水平，并且含铜化合物和配合物可以抑制酶果糖胺-3-激酶。
• Le blocage de la lysine par la réaction de M<scp>AILLARD</scp>. I. Synthèse de N-(désoxy-1-<scp>D</scp>-fructosyl-1)- et N-(désoxy-1-<scp>D</scp>-lactulosyl-1)-<scp>L</scp>-lysines
  作者：P. A. Finot、J. Mauron

  DOI：10.1002/hlca.19690520609

  日期：——

  The authors describe a specific method for the preparation of Nϵ-(1-deoxy-D-fructosyl)-L-lysine, Nα-(1-deoxy-D-fructosyl)-L-lysine, their formyl derivatives, and Nα-formyl-ϵ-(1-deoxy-D-lactulosyl)-L-lysine, as well as Nα, Nϵ-di-(1-deoxy-D-fructosyl)-L-lysine. After purification by cation-exchange chromatography using volatile pyridine-acetic acid or pyridine-formic acid buffers, these compounds are

  作者描述了一种具体的制备N for-（1-脱氧-D-果糖基）-L-赖氨酸，Nα-（1-脱氧-D-果糖基）-L-赖氨酸，它们的甲酰基衍生物和Nα-甲酰基的方法。 -ϵ-（1-脱氧-D-乳糖基）-L-赖氨酸，以及Nα，Nϵ-二-（1-脱氧-D-果糖基）-L-赖氨酸。在使用挥发性吡啶-乙酸或吡啶-甲酸缓冲液通过阳离子交换色谱法纯化后，以纯净状态获得这些化合物。通过薄层色谱和纸电泳可以快速分离和鉴定这些赖氨酸衍生物。
• Method for reducing a susceptibility to tumor formation induced by 3-deoxyglucosone and precursors thereof
  申请人：Brown R. Truman

  公开号：US20060089316A1

  公开（公告）日：2006-04-27

  Disclosed are methods of using various compounds, which are known to bind to 3-deoxyglucosone (3DG) or precursors thereof, in order to reduce a susceptibility to tumor formation and/or to prevent or delay onset of tumor formation induced by 3DG and its precursors. Also disclosed is the reduction of 3DG levels in high fructose corn syrop so that the high fructose corn syrup is less likely to induce tumor formation.

  公开了使用各种已知与3-脱氧葡萄糖酮（3DG）或其前体结合的化合物的方法，以减少对肿瘤形成的易感性和/或预防或延迟由3DG及其前体诱导的肿瘤形成。还公开了降低高果糖玉米糖浆中3DG水平的方法，以使高果糖玉米糖浆不太可能诱导肿瘤形成。
• Albumin-binding compounds that prevent nonenzymatic glycation and that may be used for treatment of glycation-related pathologies
  申请人：——

  公开号：US20010034359A1

  公开（公告）日：2001-10-25

  The present invention is directed to compositions that inhibit the nonenzymatic glycation of albumin, as well as methods of using compounds that inhibit albumin glycation for the treatment of glycation-related pathologies.

  本发明涉及抑制白蛋白非酶促糖基化的组合物，并使用抑制白蛋白糖基化的化合物治疗糖基化相关病理的方法。