DISTINGUISHING ISOBARIC AMINO-ACIDS IN SEQUENCE-ANALYSIS OF CYCLOSPORINES BY FAST-ATOM-BOMBARDMENT AND LINKED-SCAN MASS-SPECTROMETRY

An analytical protocol suggested previously for the mass spectrometric sequence analysis of cyclosporins was extended by addition of methods for discrimination among isobaric amino acids differing either in the nature of the side-chain or N-substitution, The former goal was achieved by comparison of B/E linked-scan mass spectra of corresponding collisionally activated immoninm ions with those of standard amino acids and the latter by comparison of B/E fragment ion spectra of [M + H](+) and [M(d) + H-2](+) ions. The use of the improved protocol is illustrated by the structure elucidation of a novel natural cyclosporin, [Leu(9)]CS.