α-conotoxin AuIB globular | 216299-21-7

• 物质功能分类: 有机原料 - 螺环化合物
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: α-conotoxin AuIB globular
• 英文别名: AuIB globular；Alpha-Conotoxin AuIB；2-[(1R,6R,9S,12S,18S,21S,24S,27S,30R,33S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-18-(2-amino-2-oxoethyl)-27-benzyl-6-carbamoyl-21-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-45-[(4-hydroxyphenyl)methyl]-24-methyl-8,11,17,20,23,26,29,32,38,44,47,50,52-tridecaoxo-3,4,55,56-tetrathia-7,10,16,19,22,25,28,31,37,43,46,49,51-tridecazapentacyclo[28.20.7.012,16.033,37.039,43]heptapentacontan-9-yl]acetic acid
• CAS: 216299-21-7
• 化学式: C₆₅H₈₉N₁₇O₂₁S₄
• 分子量: 1572.79
• InChiKey: SVNSCQIKKAACJG-SBLJLSJOSA-N

物化性质

• 沸点：
  2035.8±65.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -7.4
• 重原子数：
  107
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  692
• 氢给体数：
  18
• 氢受体数：
  26

制备方法与用途

生物活性

α-Conotoxin AuIB 是一种有效的选择性 α3β4 烟碱乙酰胆碱受体 (nAChR) 拮抗剂，α-Conotoxin AuIB 阻断非洲爪蟾卵母细胞中表达的 α3β4 nAChRs，IC50 为 0.75 μM。

靶点

IC50: 0.75 μM (α3β4 nAChR; in Xenopus oocytes)

体外研究

α-Conotoxin AuIB blocks the α3β4 receptor with >100-fold higher potency than other receptor subunit combinations, including α2β2, α2β4, α3β2, α4β2, α4β4, and α1β1γδ.

反应信息

• 作为反应物：
  描述：

  α-conotoxin AuIB globular 在 谷胱甘肽 作用下， 反应 3.0h， 生成 α-conotoxin AuIB bead 、 α-conotoxin AuIB ribbon
  参考文献：
  名称：

  Solving the α-Conotoxin Folding Problem: Efficient Selenium-Directed On-Resin Generation of More Potent and Stable Nicotinic Acetylcholine Receptor Antagonists

  摘要：

  alpha-Conotoxins are tightly folded miniproteins that antagonize nicotinic acetylcholine receptors (nAChR) with high specificity for diverse subtypes. Here we report the use of selenocysteine in a supported phase method to direct native folding and produce alpha-conotoxins efficiently with improved biophysical properties. By replacing complementary cysteine pairs with selenocysteine pairs on an amphiphilic resin, we were able to chemically direct all five structural subclasses of alpha-conotoxins exclusively into their native folds. X-ray analysis at 1.4 angstrom resolution of alpha-selenoconotoxin PnIA confirmed the isosteric character of the diselenide bond and the integrity of the alpha-conotoxin fold. The alpha-selenoconotoxins exhibited similar or improved potency at rat diaphragm muscle and alpha 3 beta 4, alpha 7, and alpha 1 beta 1 delta gamma nAChRs expressed in Xenopus oocytes plus improved disulfide bond scrambling stability in plasma. Together, these results underpin the development of more stable and potent nicotinic antagonists suitable for new drug therapies, and highlight the application of selenocysteine technology more broadly to disulfide-bonded peptides and proteins.

  DOI：

  10.1021/ja910602h