5-aminopentanyl α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→3)]-α-D-glucopyranosyl-(1→2)-α-D-glucopyranoside | 1334540-14-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-aminopentanyl α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→3)]-α-D-glucopyranosyl-(1→2)-α-D-glucopyranoside
• 英文别名: alpha-L-Rhap-(1->3)-[alpha-L-Rhap-(1->3)-beta-D-Glcp-(1->4)]-alpha-D-Glcp-(1->2)-alpha-D-GlcpO[CH2]5NH2；(2S,3R,4R,5R,6S)-2-[(2S,3R,4S,5R,6R)-2-[(2R,3R,4R,5R,6R)-6-[(2S,3R,4S,5S,6R)-2-(5-aminopentoxy)-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-5-hydroxy-2-(hydroxymethyl)-4-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-methyloxane-3,4,5-triol
• CAS: 1334540-14-5
• 化学式: C₃₅H₆₃NO₂₄
• 分子量: 881.878
• InChiKey: VMKYJNNYYJNBRB-YYUHOULWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.8
• 重原子数：
  60
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  402
• 氢给体数：
  15
• 氢受体数：
  25

反应信息

• 作为产物：
  描述：

  N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-O-benzyl-β-D-glucopyranosyl-(1→4)-[2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)]-2,6-di-O-benzyl-α-D-glucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-D-glucopyranoside 在 sodium methylate 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.5h， 以60%的产率得到5-aminopentanyl α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→3)]-α-D-glucopyranosyl-(1→2)-α-D-glucopyranoside
  参考文献：
  名称：

  [EN] OLIGOSACCHARIDES AND OLIGOSACCHARIDE-PROTEIN CONJUGATES DERIVED FROM CLOSTRIDIUM DIFFICILE POLYSACCARIDE PS-I, METHODS OF SYNTHESIS AND USES THEREOF, IN PARTICULAR AS VACCINES AND DIAGNOSTIC TOOLS
  [FR] OLIGOSACCHARIDES ET CONJUGUÉS D'OLIGOSACCHARIDES-PROTÉINES PROVENANT DE POLYSACCARIDES PS-I DE CLOSTRIDIUM DIFFICILE, LEURS PROCÉDÉS DE SYNTHÈSE ET D'UTILISATION, EN PARTICULIER EN TANT QUE VACCINS ET OUTILS DE DIAGNOSTIC

  摘要：

  该发明涉及一种合成的寡糖，代表Clostridium difficile糖聚合物PS-I的重复单元的一部分，并具有五糖基序列a-L-Rhap-（1→3）-β-D-Glcp-（1→4）-[a-L-Rhap-（1→3]-a-D-Glcp-（1→2）-a-D-Glcp或其合成片段或衍生物。优选，所述的合成寡糖至少带有一个连接子L，用于与载体蛋白共轭或固定在表面上。该发明的进一步方面涉及有利的合成所述合成寡糖和寡糖-蛋白共轭的方法，以及它们的用途，特别是作为疫苗和诊断工具。

  公开号：

  WO2013017254A1

文献信息

• Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit
  作者：Christopher E. Martin、Markus W. Weishaupt、Peter H. Seeberger

  DOI：10.1039/c1cc13614c

  日期：——

  Clostridium difficile strain ribotype 027 is a hypervirulent pathogen that is responsible for recent, severe outbreaks of serious nosocomial infections. As a foundation for the development of a preventative carbohydrate-based vaccine, we have synthesized a pentasaccharide cell wall repeating unit from PS-I unique to this strain, by the linear assembly of four monosaccharide building blocks.

  克劳斯特里迪姆·迪菲西尔株核糖型027是一种高度毒力病原体，导致了最近严重的医院感染暴发。作为开发基于碳水化合物的预防性疫苗的基础，我们通过对四种单糖构件进行线性组合，合成了该株特有的PS-I五糖细胞壁重复单元。
• Oligosaccharides and oligosaccharides-protein conjugates derived from clostridium difficile polysaccharide PS-I, methods of synthesis and uses thereof, in particular as vaccines and diagnostic tools
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2554549A1

  公开（公告）日：2013-02-06

  The invention relates to a synthetic oligosaccharide representing part of the repeating unit of the Clostridium difficile glycopolymer PS-I and having the sequence of the pentasaccharide α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-D-Glcp or a synthetic fragment or derivative thereof. Preferably, the claimed synthetic oligosaccharide bears at least one linker L for conjugation to a carrier protein or for immobilization on a surface. Further aspects of the invention relate to advantageous methods for synthesizing said synthetic oligosaccharide and oligosaccharide-protein conjugate as well as to uses thereof, in particular as vaccines and diagnostic tools. A preferred method for synthesizing the pentasaccharide is shown below.

  该发明涉及一种合成的寡糖，代表Clostridium difficile糖聚合物PS-I的重复单元的一部分，并具有五糖基序列α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-D-Glcp或其合成片段或衍生物。优选，所述的合成寡糖至少带有一个连接体L，用于与载体蛋白结合或在表面上固定。该发明的其他方面涉及有利的合成所述合成寡糖和寡糖-蛋白共轭物的方法，以及它们的用途，特别是作为疫苗和诊断工具。下面显示了一种合成五糖基的首选方法。
• Clostridium difficile PSI polysaccharide: synthesis of pentasaccharide repeating block, conjugation to exotoxin B subunit, and detection of natural anti-PSI IgG antibodies in horse serum
  作者：Yuening Jiao、Zuchao Ma、Doug Hodgins、Brittany Pequegnat、Lisa Bertolo、Luis Arroyo、Mario A. Monteiro

  DOI：10.1016/j.carres.2013.03.018

  日期：2013.8

  unit carrying a linker at the reducing end, α-l-Rhap-(1→3)-β-d-Glcp-(1→4)-[α-l-Rhap-(1→3)]-α-d-Glcp-(1→2)-α-d-Glcp-(1→O(CH2)5NH2, was achieved by a linear synthesis strategy from four monosaccharide building blocks. The synthesized PSI pentasaccharide was conjugated to a subunit of C. difficile exotoxin B yielding a potential dual C. difficile vaccine. More significantly, sera from healthy horses were

  艰难梭菌是人类与抗生素相关的腹泻的最常见原因，并可能导致死亡。以前，我们发现艰难梭菌表达三种多糖，分别称为PSI，PSII和PSIII。现已确定，PSII是一种保守的抗原，大量存在于艰难梭菌的细胞表面和生物膜上。相反，PSI和PSIII的表达似乎是随机过程。在这项工作中，PSI五糖重复单元的全部化学合成在还原端带有一个连接子，即α-1-Rhap-（1→3）-β-d-Glcp-（1→4）-[α-1 -Rhap-（1→3）]-α-d-Glcp-（1→2）-α-d-Glcp-（1→O（CH2）5NH2，是通过线性合成策略由四个单糖结构单元实现的。将合成的PSI五糖缀合到艰难梭菌外毒素B的一个亚基上，产生潜在的双重C. 难疫苗。更重要的是，显示出健康马的血清中含有天然抗PSI IgG抗体，该抗体可检测合成的非磷酸化PSI重复序列和天然PSI多糖，对天然PSI多糖的识别度稍高。
• Immunological Evaluation of a Synthetic Clostridium difficile Oligosaccharide Conjugate Vaccine Candidate and Identification of a Minimal Epitope
  作者：Christopher E. Martin、Felix Broecker、Matthias A. Oberli、Julia Komor、Jochen Mattner、Chakkumkal Anish、Peter H. Seeberger

  DOI：10.1021/ja401410y

  日期：2013.7.3

  Clostridium difficile is the cause of emerging nosocomial infections that result in abundant morbidity and mortality worldwide. Thus, the development of a vaccine to kill the bacteria to prevent this disease is highly desirable. Several recently identified bacterial surface glycans, such as PS-I and PS-II, are promising vaccine candidates to preclude C difficile infection. To circumvent difficulties with the generation of natural PS-I due to its low expression levels in bacterial cultures, improved chemical synthesis protocols for the pentasaccharide repeating unit of PS-I and oligosactharide substructures were utilized to produce large quantities of well-defined PS-I related glycans. The analysis of stool and serum samples obtained from C. difficile patients using glycan microarrays of synthetic oligosaccharide epitopes revealed humoral immune responses to the PS-I related glycan epitopes. Two different vaccine candidates were evaluated in the mouse model. A synthetic PS-I repeating unit CRM197 conjugate was immunogenic in mice and induced immunoglobulin class switching as well as affinity maturation. Microarray screening employing PS-I repeating unit substructures revealed the disaccharide Rha-(1 -> 3)-Glc as a minimal epitope. A CRM197-Rha-(1 -> 3)-Glc disaccharide conjugate was able to elicit antibodies recognizing the C. difficile PS-I pentasaccharide. We herein demonstrate that glycan microarrays exposing defined oligosaccharide epitopes help to determine the minimal immunogenic epitopes of complex oligosaccharide antigens. The synthetic PS-I pentasaccharide repeating unit as well as the Rha-(1 -> 3)-Glc disaccharide are promising novel vaccine candidates against C difficile that are currently in preclinical evaluation.