Single bead parallel synthesis and screening.
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.
Vetter
D
D
Graffinity Pharmaceutical Design GmbH, Heidelberg, Germany.
Thamm
A
A
Schlingloff
G
G
Schober
A
A
D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D036103:Nanotechnology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D012825:Silicon / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry
D019151:Peptide Library; D010455:Peptides; D012235:Rhodamines; D013917:Thrombin; D012825:Silicon