Digital light-directed synthesis. A microarray platform that permits rapidreaction optimization on a combinatorial basis

Solution reactions using photogenerated reagents (Gao, X.; Yu, P.; LeProust , E.; Sonigo, L.; Pellois, J. P.; Zhang, H. J. Am. Chem. Sec. 1998, 120, 12 698) are a potentially powerful means for combinatorial parallel synthesis of addressable molecular microarrays. In this report, we demonstrate that t his chemistry permits combinatorial screening of reaction conditions on a m icroarray platform. Using this method of optimization and our reaction appa ratus, efficient photogenerated acids and reaction conditions suitable for removal of the acid labile protection group on 5'-O of nucleotides are iden tified in a short period of time. The chemistry platform demonstrated opens new avenues for rapid, simultaneous investigation of multiple reactions us ing different reagents and reaction parameters directly on a solid support (e.g., a glass plate). The combinatorial screening method described may be extended to include general organic reactions employing photogenerated and conventional reagents as well as a microarray reaction device. This should be especially valuable for efficient synthesis of addressable organic compo und libraries.