P-67 光親和型SPRイメージング法と化合物アレイを用いたケミカルバイオロジー研究 : リンカーの改良によって可能となった小分子化合物-タンパク質相互作用検出(ポスター発表の部)

概要

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SPR imaging technique has been used to observe multiple interactions between non-labeled biological molecules and surface-bound molecules. We have recently developed a "photoaffinity-linking" protocol to enable the introduction of structurally diverse small-molecules on solid surface in a functional-independent manner. Here we describe the improvement of the photoaffinity thiol linker of our SPR imaging platform, which enabled us to determine the binding site of p62/SQSTM1 to p38 mitogen-activated protein (MAP) kinase. SPR imaging experiments using a new photoaffinity linker 2 to immobilize the peptides derived from p62 on gold substrate indicated that the domain comprising amino acids 164-190 of p62 binds to p38 directly. These SPR analysis data and empirical biologic data revealed that the binding site of p62 to p38 is the domain corresponding to 173-182. We also describe a screening study of small-molecules which have inhibitory activity of tau aggregation. Starting with 2011 compounds, 202 compounds were identified as tau-binding compounds by chemical array screening. Among them, 53 compounds were detectable by our photoaffinity SPR platform using linker 3. Finally, it was revealed that 42 compounds have inhibitory activity for tau aggregation.
天然有機化合物討論会の論文
2008-09-01