Light-Directed, Spatially Addressable Parallel Chemical Synthesis

TLDR

Binary masking yields 2ⁿ compounds in n steps, and high‑density light‑directed arrays offer rich chemical diversity for discovering ligands and elucidating molecular interactions. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. Solid‑phase chemistry, photolabile protecting groups, and photolithography were combined to achieve light‑directed, spatially addressable parallel synthesis yielding a highly diverse set of products, as shown by the synthesis of a dinucleotide.

Abstract

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 2 n 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.