I have a large synthetic peptide (>8 kDa) I wish to analyze by MS (MALDI). However, getting in-tact MW for this peptide is hopeless, as our instrument sensitivity falls off dramatically > 3 kDa
I'm considering a tryptic digest. If LYS residues are rendered unrecognizable by trypsin, hydrolysis only at ARG residues will yield 4 fragments of ideal size for detection.
Is acetylation with acetic anhydride the best option for modifying lys?
I have read that free cys can also become acetylated during this process, so preliminary carboxymethylation of cys was recommended. Is this so?