An alternative method to enzymatic digestion for protein identification by
mass spectrometry has been developed that is based on chemical cleavage by
formic acid. This method was tested on gel-purified apomyoglobin and BSA, a
s well as unknown proteins that cofractionate with Ty1-virus-like particles
from Saccharomyces cerevisiae. Cleavage at aspartyl residues was found to
be efficient and specific, and this specificity of cleavage lent itself eas
ily to database searches. Parallel digestions using trypsin were also perfo
rmed. The formic acid cleavage method generated comparable or better result
s than tryptic digestion for protein identification.