Abstract
A novel one-bead one-compound (OBOC) dual ring-opening/cleavage approach for cyclic peptide sequencing was developed. The method selectively modifies serine, cysteine, threonine, and/or glutamic acid to an oxazolidinone-derived moiety, thereby increasing the susceptibility of the modified peptide backbone toward hydrolysis. The resulting linear peptide was then sequenced in 1 min by tandem mass spectrometry on a quadrupole time-of-flight instrument incorporating two-dimensional liquid chromatography and ion mobility spectrometry separation. To evaluate this approach, a library of cyclic peptides was successfully sequenced with 98% overall accuracy, demonstrating its robustness and broad substrate scope.
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