Chemical construction and structural permutation of neurotoxic natural product, antillatoxin: importance of the three-dimensional structure of the bulky side chain

DOI Web Site Web Site PubMed 被引用文献5件 参考文献19件
  • INOUE Masayuki
    Graduate School of Pharmaceutical Sciences, The University of Tokyo

この論文をさがす

抄録

Antillatoxin 1 is a unique natural product that displays potent neurotoxic and neuritogenic activities through activation of voltage-gated sodium channels. The peptidic macrocycle of 1 was attached to a side chain with an exceptionally high degree of methylation. In this review, we discuss the total synthesis and biological evaluation of 1 and its analogues. First we describe an efficient synthetic route to 1. This strategy enabled the unified preparation of nine side chain analogues. Structure-activity relationship studies of these analogues revealed that subtle side chain modification leads to dramatic changes in activity, and detailed structural analyses indicated the importance of the overall size and three dimensional shape of the side chain. Based on these data, we designed and synthesized a photoresponsive analogue, proving that the activity of 1 was modulated via a photochemical reaction. The knowledge accumulated through these studies will be useful for the rational design of new tailor-made molecules to control the function and behavior of ion channels.

収録刊行物

被引用文献 (5)*注記

もっと見る

参考文献 (19)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ