ABSTRACT
In terms of structural change, L → D chirality inversion of an amino acid residue side chain in polypeptides is the most subtle posttranslational modication.1 It presents a signicant challenge for detection by tandem mass spectrometry (MS/MS), as it does not result in either molecular mass deviation or appearance of specic fragment masses. When all amino acids in the polypeptide chain invert their chirality, direct MS/MS distinguishing becomes impossible. However, an MS/MS solution exists if one or several residues in the polypeptide chain are epimerized (epimers are diastereomers that differ in conguration of only one stereogenic center), while the rest preserve their chiral orientation. As early as 1985, Tabet et al. have differentiated diastereoisomers of acetylated diphenylananine peptide by tandem mass spectrometry.2 This and all subsequent chiral differentiation efforts have been based exclusively on fragment abundances. In this article we describe direct MS/MS approaches for chiral recognition in peptides. Differentiation by tandem MS of peptide-molecule clusters is discussed in other chapters of this book.
