<< This is supposedly caused by reaction of the reagent with the
alpha amino group of the N-terminal amino acid followed by cyclization
and cleavage during the R3 treatment in the begin cycle. >>
I don't have David's article at hand so he may have mentioned this, but it has
always been my belief that this fraying of the amino terminus occurs because
the vinyl pyridine reaction creates a secondary amine at the amino terminus.
It is little known, but has been in the literature for years, that a secondary
amine at the amino terminus can produce cleavage of the first amino acid
during coupling. If the excess vinyl pyridine is removed before coupling,
fraying only occurs for that first amino acid; if it is still present when the
basic coupling conditions are introduced, cleavage can occur, followed by
reaction of the new amino terminus with either PITC or vinyl pyridine,
extending the raggedness.
The reference for coupling and cleavage of secondary amino termini goes back
to work on E. Coli ribosomal proteins in the seventies out of the Wittman-
Liebold lab in Berlin. All my files are in a box somewhere, but I seem to
recall that it was published in FEBS Letters on ribosomal protein S11, which
starts with an N-methyl alanine.
Michael F. Rohde