Fodor S P, Read J L, Pirrung M C, Stryer L, Lu A T, Solas D
Affymax Research Institute, Palo Alto, CA 94304.
Science. 1991 Feb 15;251(4995):767-73. doi: 10.1126/science.1990438.
Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one of many possible combinatorial synthesis strategies, yields 2n compounds in n chemical steps. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. High-density arrays formed by light-directed synthesis are potentially rich sources of chemical diversity for discovering new ligands that bind to biological receptors and for elucidating principles governing molecular interactions. The generality of this approach is illustrated by the light-directed synthesis of a dinucleotide. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices.
固相化学、光不稳定保护基团和光刻技术相结合，实现了光导向、空间可寻址的平行化学合成，从而产生了高度多样化的化学产物。二元掩膜是众多可能的组合合成策略之一，在n个化学步骤中可产生2ⁿ种化合物。通过十个步骤合成了一个包含1024种肽的阵列，并通过落射荧光显微镜检测了其与单克隆抗体的相互作用。光导向合成形成的高密度阵列可能是丰富的化学多样性来源，可用于发现与生物受体结合的新配体，并阐明分子相互作用的原理。二核苷酸的光导向合成说明了这种方法的通用性。复杂化合物的空间定向合成也可用于器件的微制造。
