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

A strategy is presented for the determination of amino-acid sequences of cy clodepsipeptide antibiotics. A highly specific sodium-ion interaction with the backbone lactone opens the depsipeptide ring to form a linear acylium i on or isomeric equivalent. When activated by high energy collisions on a ta ndem mass spectrometer or by low energy collisions on an ion trap, the acyl ium 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. Interfere nces from indiscriminate ring opening at backbone amide bonds are eliminate d. The method is suited to the structural analyses of various cyclodepsipep tides, including those with linear peptide moieties. Results are presented for beauvericin, didemnin B, and enniatin B1, representing the three common ly encountered structural variations in cyclodepsipeptide antibiotics. (C) 1999 Elsevier Science B.V.