Trityl Tags for Encoding in Combinatorial Synthesis

New tags and an encoding strategy for combinatorial synthesis are described. Combinatorial libraries of short oligonucleotides attached to TentaGel beads were synthesised by a split-and-mix strategy using 5′-DMTr or 5′-Fmoc-protected nucleoside phosphoramidites. Trityl moieties with different masses were used to tag the nature and position of monomer units (bases) coupled at each step in the synthesis. Beads with a specific oligonucleotide were selected by hybridisation from combinatorial libraries. Tags orthogonal to the added nucleotides were produced by coupling amines of different molecular masses to an activated carboxyl group(s) on the trityl moiety. The tags may be released from the support by an acidic treatment or laser irradiation and then analysed by (MA)LDI-TOF. These properties make trityl-based tags promising for encoding in strategies not involving strong acids, such as oligonucleotide and peptide synthesis and small molecule combinatorial libraries.