4/6[A10L]PnIA | 1062091-87-5

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: 4/6[A10L]PnIA
• CAS: 1062091-87-5
• 化学式: C₅₉H₉₂N₁₈O₂₀S₄
• 分子量: 1501.75
• InChiKey: GCWXVQJOYLNRET-DNMWBBKNSA-N

反应信息

• 作为产物：
  描述：

  在 盐酸 、 碘 作用下， 以 甲醇 、 水 为溶剂， 反应 0.08h， 生成 4/6[A10L]PnIA
  参考文献：
  名称：

  Molecular Engineering of Conotoxins: The Importance of Loop Size to α-Conotoxin Structure and Function

  摘要：

  alpha-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). The majority of currently characterized alpha-conotoxins have a 4/7 loop size, and the major features of neuronal alpha-conotoxins include a globular disulfide connectivity and a helical structure centered around the third of their four cysteine residues. In this study, a novel "molecular pruning" approach was undertaken to define the relationship between loop size, structure, and function of a-conotoxins. This involved the systematic truncation of the second loop in the a-conotoxin [A10L]PnIA [4/7], a potent antagonist of the alpha 7 nAChR. The penalty for truncation was found to be decreased conformational stability and increased susceptibility to disulfide bond scrambling. Truncation down to 4/4[A10L]PnIA maintained helicity and did not significantly reduce electrophysiological activity at alpha 7 nAChRs, whereas 4/3[AIOL]PnIA lost both alpha 7 nAChR activity and helicity. In contrast, all truncated analogues lost similar to 100-fold affinity at the AMP, a model protein for the extracellular domain of the nAChR. Docking simulations identified several hydrogen bonds lost upon truncation that provide an explanation for the reduced affinities observed at the alpha 7 nAChR and AChBP.

  DOI：

  10.1021/jm800278k