The stimulating adventure of KRN 7000 |
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Authors: | Banchet-Cadeddu Aline Hénon Eric Dauchez Manuel Renault Jean-Hugues Monneaux Fanny Haudrechy Arnaud |
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Institution: | ICMR-CNRS UMR 6229, Université de Reims Champagne-Ardenne, BP 1039, 51687 REIMS cedex, France. A.Banchet@laposte.net |
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Abstract: | 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. |
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