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Abstract

Microstructured silicon wafers were employed as miniaturized solid-phase reaction vessels as well as miniaturized micro titer plates. Employing piezoelectric drop-on-demand liquid jets, a combinatorial library of 256 Peptides was synthesized on single beads. The synthesis protocol was associated to the location in the silicon nano-well arrangement. Products were photolytically cleaved in the same well that was used for synthesis and subsequently interrogated for thrombin inhibition in a homogeneous competition assay. The assay procedure was based on drop-on-demand liquid delivery and laser induced fluorescence imaging. The novel format proved useful for the integration of both synthesis and screening into one platform, a prerequisite for an iterative, evolutionary approach towards drug discovery.

Microreactor Array Assembly, Designed for Diversity Oriented Synthesis Using a Multiple Core Structure Library on Solid Support

“…The result of the subsequent chemical assembly is a two-dimensional array of tethered substances with known reaction history for each compound [16, 33 -35]. Most of these approaches are restricted to oligomer synthesis or special chemical protocols which are close to the conditions for peptide chemistry [13,36]. We have demonstrated before, that peptide synthesis can be performed in a 100 nL volume scale at 40 8C in an open system [36].…”

“…Most of these approaches are restricted to oligomer synthesis or special chemical protocols which are close to the conditions for peptide chemistry [13,36]. We have demonstrated before, that peptide synthesis can be performed in a 100 nL volume scale at 40 8C in an open system [36]. Evaporative loss of solvents with low vapor pressure like Dimethylformamide (DMF) was controlled by periodical replacement of the solvent.…”