The stimulating adventure of KRN 7000
The stimulating adventure of KRN 7000
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DOI：
10.1039/c0ob00975j
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Haudrechy, Arnaud
中科院分区：
文献类型：
--
作者：
Banchet-Cadeddu, Aline;Henon, Eric;Haudrechy, Arnaud
与CD1d蛋白相关的KRN 7000是一种有效的合成α -半乳糖神经酰胺，已知可激活不变的NKT免疫细胞。这种刺激随后导致不同细胞因子的产生，调节T(H)1/T(H)2免疫反应平衡，参与预防多种病理，如自身免疫性疾病和癌症。为了选择性地诱导T(H)1或T(H)2型细胞因子的产生，人们已经做出了各种各样的努力来合成简单和更功能化的类似物。自发现KRN 7000以来，结构-活性关系、晶体学和建模研究已经指出了几种GalCer类似物在选择性生物活性方面的潜力，并强调了有趣的元素，以便更好地理解免疫iNKT细胞的识别和激活机制。通过展示最新的类似物库，收集晶体学和分子建模方面的最新突破，并将它们与现有的生物学结果联系起来，我们希望这篇综述将突出并帮助科学界进行KRN研究。
Associated with the CD1d protein, KRN 7000, a potent synthetic alpha-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a T(H)1/T(H)2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce T(H)1 or T(H)2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.