49(P-13) 官能基非依存型低分子アレイの作成と評価(ポスター発表の部)

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Small-molecule microarray has been developed as a new technology to investigate ligand-protein interactions en masse. To construct the microarrays, synthetic small-molecule library has been prepared by solid-phase split pool synthesis and diversity-oriented synthetic methodology, and immobilized on solid surfaces by using selective coupling reactions. Although this is well suitable method for immobilizing library of synthetic small molecules that have a certain functional group, it is expected to be difficult to immobilize structurally diverse small molecules including natural products library by using this method. Even though the small molecules could be introduced on the solid surfaces, a certain area of the small molecule faces toward the solid surface, and therefore some of the immobilized compounds will not come into contact with the relevant binding proteins. As it is difficult to predict the binding domain of small molecules that interact with unknown proteins, this poses a major drawback to such studies, especially when the goal is to discover new target proteins for small molecules using microarray technology. To address the problem, we developed conceptually new immobilization method, namely, functional group independent immobilization using photoaffinity reaction. In the present method, photoreactive aryl diazirines are first immobilized on glass slide via polyethylene glycol linker, and small molecules were printed on the diazirine-coated glass slide. Photoreactive aryl diazirines should be promoted upon irradiation to highly reactive species, which in turn bind or insert irreversibly to the small molecules printed on the glass slide. To demonstrate our concept, structurally diverse organic molecules were immobilized on the diazirine-coated glass slide. Specific interactions between the small molecules and labeled proteins were successfully detected on the slides. The results of these studies will be presented.
天然有機化合物討論会の論文
2003-09-01

49(P-13) 官能基非依存型低分子アレイの作成と評価(ポスター発表の部)

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