Bacterial β-peptidyl aminopeptidases: on the hydrolytic degradation of β-peptides
A brief survey of the history of custom peptide synthesisfrom Theodore Curtius to Emil Fischer to Bruce Merrifield is first presented.The discovery and development of peptide ligation, i.e. of actual chemical synthesis of proteins are described.In the main chapter, a??Synthesis of Proteins by Chemical Ligationa?? a detailed discussion of the principles, reactivities and mechanisms involved in the various coupling strategies now applied (ligation, chemical ligation, native chemical ligation) is given.These include coupling sites with cysteine and methionine (as well as the seleno analogs), histidine, glycine and pseudo-prolines, a??unrestricteda?? amino-acid residues (using the Staudinger reaction), as well as solid-phase segment coupling by thioligation of unprotected peptides.In another section, a??Synthesis of ?2-peptides by Thioligationa??, couplings involving ?22- and ?23-peptides are described (with experimental details). The special chemical and biological features of custom peptide synthesis have been investigated intensively during recent years.Many studies emphasize the restricted biodegradability and the high metabolic stability of this class of compounds.β-Peptidyl aminopeptidases form the first family of enzymes that hydrolyze a variety of short β-peptides and β-amino-acid-containing peptides.All representatives of this family were isolated from Gram-negative bacteria.The substrate specificities of the peptidases vary greatly, but the enzymes have common structural properties, and a similar reaction mechanism can be expected. This review gives an overview on the β-peptidyl aminopeptidases with emphasis on their biochemical and structural properties.Their possible physiological function is discussed.Functionally and structurally related enzymes are compared to the β-peptidyl aminopeptidases.