Gas‐phase reactivity of protonated cyclodepsipeptidic toxins: The study of a systematic fragmentation pathway under fast‐atom bombardment desorption

Abstract

A systematic pathway of fragmentation for several protonated cyclohexadepsipeptides is demonstrated by positive-ion fast-atom bombardment linked-scan mass spectrometry. It involves classical sequential acylium and immonium ions, but also, unusual fragment ions characteristic of this family of compounds.Since fast-atom bombardment (FAB) and liquid secondary ion mass spectrometry (LSIMS) ionization techniques have been introduced, structural analyses of linear and cyclic peptides have improved. 1 . 2 3 3 Thus, numerous examples of primary structure elucidation have been r e p~r t e d .~. ' In a recent review, Traldi gives important views of tandem mass spectrometry for cyclo(depsi)peptides.6 More recently, an exhaustive review from Eckart summarizes all the strategies developed for sequencing cy~lopeptides.~ In the case of cyclodepsipeptides, Lange et al. proposed two methodologies to determine the primary structure of destruxins', 9, lo which are natural toxins from Metarhizium anisopliae. The first is direct sequence determination by means of sequential carboxylate anions observed in conventional negative-ion FAB mass spectra.' The second approach used positive-ion FAB tandem mass spectrometry with low9 and high" energy collision-induced dissociation (CID). Under the latter conditions, a rapid and unambiguous sequence elucidation of destruxin-E (DTX-E) was performed by two-and three-stage tandem mass spectrometry (MS' and MS3), sequential product-ion spectra and by reaction-intermediate scanning (MS3). These strategies concerned the two most active destruxins, i.e. DTX-E and DTX-A, which possess varied biological activity and more particularly insecticidal value." Due to the high insecticidal potential, a general strategy for the synthesis of such compounds was successfully developed. 12. l3 Thus, various synthetic analogues were prepared.I4,In the present work, we attempt to show that their rapid identification becomes possible by means of characteristic and diagnostic transitions, even using a conventional (EB) double-focusing mass spectrometer.We have analysed a series of six analogues including natural and synthetic compounds (Fig. 1) by positiveion fast-atom bombardment linked-scan mass spectrometry. DTX-A, which was previously analysed on a tandem mass spectrometer: is now examined for comparison with DTX-B and the four synthetic analogues. EXPERIMENTAL ProductsDestruxins from Meturhizium anisopliae (DTX-A and DTX-B) were purified at the Institut de Chimie des Substances Naturelles, CNRS-France.I6 Synthetic analogues (Lac-6 DTX-E, Hpy-6 DTX-E, Hpp-6 DTX-E and Hpy(TMS)-6 DTX-E) were prepared at the URA-CNRS 0468-France, according to the previously published methodology.". 13, '' Glycerol (G) and mnitrobenzyl alcohol (NBA) were purchased from Prolabo (France). Xenon and helium were provided by Air Liquide (France). Mass spectrometryMass spectra were obtained on a conventional E B geometry mass spectrometer JEOL model AX-500 equipped with a DEC data system (JEOL-Europe SA, France). Ionization was realized by...

Rapid screening of destruxins by liquid chromatography/mass spectrometry

“…30 ; the superscript deÐnes the pair of amino acids between which the primary splitting takes place).31 In addition to these series, internal a destruxin-speciÐc fragment ion denoted D`was detected. 29 The ion composition of the in-source CID APCI mass spectra is qualitatively consistent with that observed in the high-energy CID spectra of [M ] H]ì ons generated by FAB ionization. 29 The reasonable abundance of sequence ions seems to be a strong advantage of the APCI mass spectra.…”

“…29 The ion composition of the in-source CID APCI mass spectra is qualitatively consistent with that observed in the high-energy CID spectra of [M ] H]ì ons generated by FAB ionization. 29 The reasonable abundance of sequence ions seems to be a strong advantage of the APCI mass spectra. The presence of corresponding immonium ions provides information on the amino acid composition of a given destruxin (Fig.…”

Comparison of collisionally activated dissociation mass spectra for the identification of cyclopeptides and cyclodepsipeptides

“…The behavior of cyclopeptides 2,[5][6][7][8][9][10][11]17,18 and cyclodepsipeptides [19][20][21][22][23][24][25][26]28 in FAB-MS has been described in the literature and the following features were reported. The initial protonation occurs preferentially on a basic site and in particular on a tertiary amide when present.…”

Sequential product‐ion spectra (MS3) with array detection and reaction‐intermediate scanning of a cyclopeptide on a five‐sector mass spectrometer

“…Sequencing destruxins or sequencing synthetic cyclohexapeptides have been demonstrated as real challenges either using lowenergy collision-induced dissociation (CID) in a QQQ instrument3 or using high-energy CID in an EB instrument . 4 Nevertheless, using first-generation product-ion spectra of these cyclic peptides, it has been observed that only sequential ions of Bi or Ai types are observed with low-energy CID, while, using highenergy CID, Bi and Ai ions are accompanied by internal fragment ions. Both analyses required numerous first-generation product-ion spectra from many precursors.…”