ICMR-CNRS UMR 6229, Université de Reims Champagne-Ardenne, BP 1039, 51687 REIMS cedex, France.
Org Biomol Chem. 2011 May 7;9(9):3080-104. doi: 10.1039/c0ob00975j. Epub 2011 Mar 11.
Associated with the CD1d protein, KRN 7000, a potent synthetic α-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.
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，已知能激活不变自然杀伤 T 细胞（iNKT）免疫细胞。这种刺激会导致产生不同的细胞因子，调节涉及预防多种疾病（如自身免疫性疾病和癌症）的 T(H)1/T(H)2 免疫反应平衡。为了合成更简单和功能化的类似物以选择性诱导 T(H)1 或 T(H)2 型细胞因子的产生，已经做出了各种努力。自 KRN 7000 发现以来，结构-活性关系、晶体学和建模研究表明，几种 GalCer 类似物在选择性生物活性方面具有潜力，并突出了一些有趣的元素，以更好地理解免疫 iNKT 细胞的识别和激活机制。通过提供最新的类似物库，收集晶体学和分子建模方面的最新突破，并将其与现有的生物学结果联系起来，我们希望这篇综述能够突出并帮助科学界进行 KRN 研究。
