Digital light-directed synthesis. A microarray platform that permits rapid reaction 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. Soc. 1998, 120, 12698) are a potentially powerful means for combinatorial parallel synthesis of addressable molecular microarrays. In this report, we demonstrate that this chemistry permits combinatorial screening of reaction conditions on a microarray platform. Using this method of optimization and our reaction apparatus, efficient photogenerated acids and reaction conditions suitable for removal of the acid labile protection group on 5'-O of nucleotides are identified in a short period of time. The chemistry platform demonstrated opens new avenues for rapid, simultaneous investigation of multiple reactions using 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 compound libraries.
LeProust
E
E
Department of Chemistry, University of Houston, Texas 77204-5641, USA.
Pellois
J P
JP
Yu
P
P
Zhang
H
H
Gao
X
X
Srivannavit
O
O
Gulari
E
E
Zhou
X
X
D002625:Chemistry, Organic / Q000379:methods*; D015195:Drug Design; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010777:Photochemistry; D012996:Solutions; D013329:Structure-Activity Relationship
D009711:Nucleotides; D012996:Solutions