We practically always see a smaller Fmoc signal on the first Pip wash
for PAl-Peg-PS resins. I was told this is due to the fact that Fmoc is
not stable on the amide linker, and falls off with time, leaving free
amines. Thus what you are seeing is the residual Fmoc (usually about 25%
of the expected signal). This does not seem to affect the resin
substitution however and after the first coupling cycle you see the Fmoc
signal deriving from the effective substitution, which normally remains
stable unless you have problem couplings. We have also had problems with
C-terminal Cys residues, but this normally comes from cleavage at the
end of synthesis, a higher tendency to racemize (preactivated
Fmoc-Cys-Opfp could be preferable in this case)and purification
problems, not to difficult coupling.
Bye, Alex