Collision-induced dissociation of protonated MK-0991: Novel ring opening of a cyclic hexapeptide in the gas phase

Electrospray ionization tandem mass spectrometry was applied to probe the c ollision-induced dissociation (CID) of protonated MK-0991 {(4R,5S)-5-[(2-am inoethyl)amino]-N-2-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-L-ornithyl-L -threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-(4-hydroxyphenyl)wL threon yl-threo-3-hydroxy-L-ornithyl-trans-3-hydroxy-L-proline cyclic (6-1)-peptid e} in the gas phase; MK-0991 is a newly developed, broad-spectrum pneumocan din antifungal drug. The study showed that protonated MK-0991 (m/z 1094) un dergoes specific ring opening under the CID conditions to form two protonat ed linear peptides at mit 1076 and 1034, This is different from the commonl y observed ring opening of a cyclic peptide that occurs by the cleavage of the N-acyl bonds in many places on the peptide backbone. The structures of the two linear peptides were elucidated on the basis of their tandem mass s pectra, The results strongly indicate that the specific ring opening of MK- 0991 is affected by the ethylenediamine side-chain formed from the modifica tion of one of the ornithine amino acids in this cyclic hexapeptide. Copyri ght (C) 1999 John Wiley & Sons, Ltd.