Application of time-of-flight secondary ion mass spectrometry toin situ monitoring of solid-phase peptide synthesis on the MultipinTM system

Abstract

In the rapidly growing field of combinatorial chemistry, the Multipin approach has been used for rapid and efficient multiple parallel syntheses 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 relation to a lead structure or for the generation of parallel libraries involving complex multistep chemistries. In all cases, direct in situ monitoring of support-bound products would be highly valuable. In this work, time-of-flight secondary ion mass spectrometry was applied to the analysis of support-bound intermediates. The analytical method was applied to a range of crowns loaded with various dipeptides. The solid support was subjected to primary ion bombardment and characteristic ions indicative of both the peptide chain and the polymeric support were unambiguously identified. Analysis could be performed at any stage of the synthesis, and as the method is effectively non-destructive, the analyzed crowns could be further used to prepare target compounds. © 1998 John Wiley & Sons, Ltd.