APPLICATION OF TIME-OF-FLIGHT SECONDARY-ION MASS-SPECTROMETRY TO IN-SITU MONITORING OF SOLID-PHASE PEPTIDE-SYNTHESIS ON THE MULTIPIN(TM) SYSTEM

In the rapidly growing field of combinatorial chemistry, the Multipin approach has been used for rapid and efficient multiple parallel synth eses of organic compounds. This strategy is particularly well adapted for the optimization of reaction conditions prior to chemical library syntheses, for the preparation of a wide range of compounds in relatio n to a lead structure or for the generation of parallel libraries invo lving complex multistep chemistries, In all cases, direct in situ moni toring of support-bound products would be highly valuable. In this wor k, time-of-flight secondary ion mass spectrometry was applied to the a nalysis of support-bound intermediates. The analytical method was appl ied to a range of crowns loaded with various dipeptides, The solid sup port was subjected to primary ion bombardment and characteristic ions indicative of both the peptide chain and the polymeric support were un ambiguously identified. Analysis could be performed at any stage of th e synthesis, and as the method is effectively non-destructive, the ana lyzed crowns could be further used to prepare target compounds. (C) 19 98 John Wiley & Sons, Ltd.