Fragment correlation mass spectrometry enables direct characterization of di-sulfide cleavage pathways of therapeutic peptides

Le résumé fourni par la source

Therapeutic peptides that are connected by disulfide bonds are often difficult to analyze by traditional tandem mass spec-trometry without chemical modification. Using fragment correlation mass spectrometry, we measured 56 pairs of fragment ions from an equimolar (10 µM) mixture of three cyclic peptides, with sequence coverages for octreotide, desmopressin, and the structural analog of desmopressin to be 86%, 100%, and 75%, respectively. In all detected fragment ion pairs, only 20% of the fragments are terminal ions, with most of the measured MS2 signals only made available by fragment correlation mass spectrometry. From the peak volumes in the covariance map, we calculated branching ratios of each disulfide fragmentation pathway, providing direct measures of disulfide fragmentation probabilities without altering analytes’ chemical structures.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.