Identification of alpha- and beta-hydroxy acid containing cyclodepsipeptides in natural peptide mixtures using negative ion mass spectrometry

J Am Soc Mass Spectrom. 2009 Dec;20(12):2221-8. doi: 10.1016/j.jasms.2009.08.010. Epub 2009 Aug 27.


Natural peptide libraries often contain cyclodepsipeptides containing alpha- or beta-hydroxy residues. Extracts of fungal hyphae of Isaria yield a microheterogenous cyclodepsipeptide mixture in which two classes of molecules can be identified by mass spectral fragmentation of negative ions. In the case of isaridins, which contain an alpha-hydroxy residue and a beta-amino acid residue, a characteristic product ion corresponding to a neutral loss of 72 Da is obtained. In addition, neutral loss of water followed by a 72 Da loss is also observed. Two distinct modes of fragmentation rationalize the observed product ion distribution. The neutral loss of 72 Da has also been obtained for a roseotoxin component, which is also an alpha-hydroxy residue containing cyclodepsipeptide. In the case of isariins, which contain a beta-hydroxy acid residue, ring opening and subsequent loss of the terminal residue as an unsaturated ketene fragment, rationalizes the observed product ion formation. Fragmentation of negative ions provide characteristic neutral losses, which are diagnostic of the presence of alpha-hydroxy or beta-hydroxy residues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anions
  • Complex Mixtures / analysis
  • Complex Mixtures / chemistry
  • Depsipeptides / analysis*
  • Depsipeptides / chemistry*
  • Fungal Proteins / analysis*
  • Fungal Proteins / chemistry*
  • Hydroxy Acids / analysis*
  • Hydroxy Acids / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods*


  • Anions
  • Complex Mixtures
  • Depsipeptides
  • Fungal Proteins
  • Hydroxy Acids