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 be ads were synthesised by a split-and-mix strategy using 5'-DMTr or 5' Fmoc-p rotected 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 s elected by hybridisation from combinatorial libraries. Tags orthogonal to t he added nucleotides were produced by coupling amines of different molecula r masses to an activated carboxyl group(s) on the trityl moiety. The tags m ay 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 ol igonucleotide and peptide synthesis and small molecule combinatorial librar ies. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.