Sodium-directed selective cleavage of lactones: a method for structure determination of cyclodepsipeptides

Abstract

A strategy is presented for the determination of amino-acid sequences of cyclodepsipeptide antibiotics. A highly specific sodium-ion interaction with the backbone lactone opens the depsipeptide ring to form a linear acylium ion or isomeric equivalent. When activated by high energy collisions on a tandem mass spectrometer or by low energy collisions on an ion trap, the acylium ion undergoes sequence-specific fragmentation to yield a simple product-ion mass spectrum. Fragmentation is charge-driven, and amino acid residues are sequentially deleted from the C-terminus of the acylium ion. Interferences from indiscriminate ring opening at backbone amide bonds are eliminated. The method is suited to the structural analyses of various cyclodepsipeptides, including those with linear peptide moieties. Results are presented for beauvericin, didemnin B, and enniatin B1, representing the three commonly encountered structural variations in cyclodepsipeptide antibiotics.