I guess CID and cyclic peptide ionization problems define two different problems, one is related to fragmentation pattern (collision-induced dissociation - which the problem is not clarified), and the other is related to protonation pattern...
For protonation issue;
I think the FA or AA preference of the peptides cannot be generalized as cyclic ones prefer AA rather than FA...This should be handled by interrogating the amino acid composition and sequence information of the peptide.
If the precursor intensities and charge distribution is similar after the MS2 experiment b and y - c and z ions must be also similar. Is your fragment MS profile similar, I mean all CID-produced fragments at the same masses but only the intensities are different or different fragments (ions) were collected after FA additive?
In summary, MS2 is linked to precursor formation, but ionization efficiency is not related to M2 acquisition preference but the charge transfer interaction between the modifier and target peptide/protein...
İsmail Emir Akyildiz Without knowing the amino acid composition, is it possible to conclude why would acetic acid work better than formic acid when we talk about protonation? Would could be the cause in this case? Maybe some physchem properties of acetic acid?
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