脂質と抗原提示タンパク質の相互作用の解明を目指した結合分子の合成と生物活性評価

点击翻译按钮获取中文摘要

We synthesized a novel series of lysophosphatidylethanolamine, which are derivatives of NKT activating plasmalogens (pLPE) isolated from mouse thymus. We have established SPR technique to examine the lipid-CD1d binding affinity and examined the binding affinity of the synthesized and some other intrinsic ligands with CD1d.Human CD1d-β2M was immobilized on CM5 sensor chip and ligands solution was passed through the modified surface for the binding analysis. The kinetic measurement conditions are established first using standard ligand KRN7000, then the binding affinities of the synthesized and other natural lysophospholipids. All the lysophospholipids showed moderate dissociation constants (KD = 85 -253 nM) to the hCD1d immobilized surface. Cerotic acid used as a negative control, which showed no binding affinity with CD1d modified surface. Among the phospholipids, which have either double bond or p-fluoro benzyl group in the tail, showed slightly stronger binding affinities than the saturated or unsubstituted derivatives. The connectivity of head-tail groups does not show any significance in the binding affinity except vinyl-ether connection. Absence or presence of ethanolamine group showed significant difference in the binding affinity. On the other hand, ethanolamine to choline transformation did not show any binding activity difference.