Harris Jennifer L, Winssinger Nicolas
Department of Chemistry, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Chemistry. 2005 Nov 18;11(23):6792-801. doi: 10.1002/chem.200500305.
Microarray-based technologies have attracted attention in chemical biology by virtue of their miniaturized format, which is well suited to probe ligand-protein interactions or investigate enzymatic activity in complex biological mixtures. A number of research groups have reported the preparation of surfaces on microarrays with specific functional groups to chemoselectively attach small molecules from libraries. We have developed an alternative method whereby libraries are encoded with peptide nucleic acid (PNA), such that libraries which exist as mixtures in solution self-assemble into an organized microarray through hybridization to produce readily available DNA arrays. This allows libraries synthesized by split and mix methods to be decoded in a single step. An asset of this method compared to direct spotting is that libraries can be used in solution for bioassays prior to self-assembly into the microarray format.
基于微阵列的技术凭借其小型化的形式在化学生物学领域引起了关注，这种形式非常适合探测配体 - 蛋白质相互作用或研究复杂生物混合物中的酶活性。许多研究小组报告了在微阵列上制备具有特定官能团的表面，以便化学选择性地连接文库中的小分子。我们开发了一种替代方法，通过用肽核酸（PNA）对文库进行编码，使得在溶液中以混合物形式存在的文库通过杂交自组装成有组织的微阵列，从而产生易于获得的DNA阵列。这使得通过拆分和混合方法合成的文库能够在一步中被解码。与直接点样相比，该方法的一个优点是文库可以在自组装成微阵列形式之前在溶液中用于生物测定。
