Differentiation of Positional Isomers of Hybrid Peptides Containing Repeats of β-Nucleoside Derived Amino Acid (β-Nda-) and L-Amino Acids by Positive and Negative Ion Electrospray Ionization Tandem Mass Spectrometry (ESI-MS^<i>n</i>)

Abstract

A new class of positional isomeric pairs of -Boc protected oligopeptides comprised of alternating nucleoside derived β-amino acid (β-Nda-) and L-amino acid residues (alanine, valine, and phenylalanine) have been differentiated by both positive and negative ion electrospray ionization ion-trap tandem mass spectrometry (ESI-MS(n)). The protonated dipeptide positional isomers with β-Nda- at the N-terminus lose CH(3)OH, NH(3), and C(2)H(4)O(2), whereas these processes are absent for the peptides with L-amino acids at the N-terminus. Instead, the presence of L-amino acids at the N-terminus results in characteristic retro-Mannich reaction involving elimination of imine. A good correlation has been observed between the conformational structure of the peptides and the abundance of y(n)(+) and b(n)(+) ions in MS(n) spectra. In the case of tetrapeptide isomers that are reported to form helical structures in solution phase, no y(n)(+) and b(n)(+) ions are observed when the corresponding amide -NH- participates in the helical structures. In contrast, significant y(n)(+) and b(n)(+) ions are formed when the amide -NH- is not involved in the H-bonding. In the case of tetra- and hexapeptides, it is observed that abundant b(n)(+) ions are formed, presumably with stable oxazolone structures when the C-terminus of the b(n)(+) ions possessed L-amino acid and the β-Nda- at the C-terminus appears to prevent the cyclization process leading to the absence of corresponding b(n)(+) ions.