An investigation of residue-specific contributions to peptide desorption in MALDI-TOF mass spectrometry

The MALDI-TOF mass spectra of a set of 240 analogs of the pentadecapeptide YTASARGDLAHLTTT, displaying single point replacements with all amino acids except Met, Cys and Trp, have been used to study the contribution of individual residues to peptide desorption. Replacements with non-polar aliphatic (except Ala) or aromatic residues at most positions tend to reinforce ion signals relative to the cognate sequence. Among polar residues, Arg shows also a clear tendency to enhance signal intensity at most positions. The responses recorded for replacements with a given amino acid can be averaged and normalized to give a mean response index\(\bar R_m \), which qualitatively expresses the relative contribution of that residue to the desorption of a generic peptide. HPLC analysis of the replacement set does not support a significant role of residue hydrophobicity in peptide desorption. The unique role of Arg in promoting peptide desorption may be related to a better stabilization of peptide-matrix adducts through guanidinium-carboxylate interaction.