Bergmann degradation

The Bergmann degradation begins with benzoylation at the alpha-group of a peptide and subsequent conversion to an acyl azide. yielding an unstable intermediate that rapidly rearranges to release carbon dioxide, driving the reaction forward. This leads to further rearrangement and subsequent hydrolysis, ultimately resulting in the formation of an aldehyde bearing the next amino acid residue in the sequencing series and the expulsion of the residual peptide in amide form. A mechanism has been proposed which depicts catalytic hydrogenation of the benzylurethane as a concerted rearrangement that releases carbon dioxide concomitantly with formation of the amide. ==Preparation of azide==

The aforementioned conversion to acyl azide has been carried out multifariously; Bergmann utilized methyl ester and hydrazide, whereas more recent attempts have designed methods such as: nitrosylation of N-formylaminoacyl hydrazide and subsequent substitution by sodium azide, and reaction between TMS azide and the anhydride of an amino acid. ==Applications==

The Bergmann degradation is intended for and has been used as a method for peptide sequencing. The compound 2,2-dimethyl-6-phthalimido-3-penamyl isocyanate was arrived at through various means, including the Curtius rearrangement, and it was envisioned that it could undergo the Bergmann degradation to form the desired aldehyde as well as the urea by-product. Though the Bergmann degradation was indeed possible, it was discovered that simple dilute acid hydrolysis would suffice in forming the desired product. ==Curtius rearrangement==

The Bergmann degradation makes use of the azide degradation described by the Curtius rearrangement. Curtius also attempted to degrade benzoylated amino acids; however, his method involved splitting the carbamate with strongly energetic treatment with acids, which lead to decomposition of the resultant aldehyde and acid amides. This convinced Bergmann that Curtius' azide degradation could be followed by treatment with benzyl alcohol (his carbobenzoxy method) to isolate the resultant amino acid aldehyde and residual peptide amide for sequencing purposes. ==Edman degradation==

The Edman degradation is an alternative method for peptide sequencing that cleaves amino acid residues from the N-terminus of a peptide. In 1950 Edman designed a reaction with phenylthiocyanate (the idea for which was borrowed from a 1927 study by Bergmann, Kann and Miekeley Phenylthiohydantoin is stable enough to undergo various sequencing procedures such as those which involve chromatography and mass spectrometry. Repetition of the Bergmann degradation is presumably not as straightforward, as the remaining peptide is in amide form. ==See also==