Increased efficiency in solid-phase Edman degradation of synthetic peptidyl-resins using an oxymethylphenylacetamidomethyl-linkage

Abstract

The solid-phase Edman degradation procedure as proposed by Laursen [ 1] is ideally suited to the evaluation of peptidyl-resin products resulting from Merrifield solid-phase synthesis [2,3] of peptides. Incomplete deprotection and incomplete coupling reactions which occur during synthesis have been detected using quantitative Edman degradation [4,5]. However, extended sequencing experiments were precluded, because the repetitive yield for the Edman procedure averaged 80% [5]. We have also observed repetitive yield values of 80-85% for other peptides synthesized on the same types of benzyl ester resin. In contrast, however, for recent sequence analyses of peptides which were synthesized using a resin with the -oxymethylphenylacetamidomethyl-linkage [63 repetitive yields averaged 95 + 3% (n = 11). In order to study this difference more critically, two model peptides were synthesized using two different peptidylresin linkages. Quantitative sequence analysis of these four peptidyl-resins provided direct comparisons of the influence of: (1)