title: Reaction mechanisms in peptide synthesis. Part 2. Tautomerism of the peptide bond.
abstract: We had concluded in previous work that ring opening of a 2-alkyl-5(4H)-oxazolone by water or ammonia leads to transient high-energy imidol intermediates which instantly tautomerize to the native amides. Using the MOPAC molecular orbital program, detailed geometric and energetic characteristics of the tautomerism of a peptide bond have been determined on the AM1 level. The results demonstrate that tautomerism of a peptide bond comprises a three-stage process involving three successive transition states and a bimolecular mechanism: (i) E----Z peptide bond isomerization followed by dimerization, (ii) concerted double-hydrogen exchange leading to an alpha-hydroxyimine (imidic acid) followed by splitting of the dimer, and (iii) Z----E N-methylimine inversion. While pathway (iii----ii----i) is predicted as a feasible route terminating in the formation of a peptide bond, the inverse route (iii----ii----i) is excluded as a possible initial step in the generation of a 5(4H)-oxazolone intermediate.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Ottawa, Ont., Canada.
authors.forename: J
authors.initials: J
authors.lastname: Ciarkowski
authors.forename: F M
authors.initials: FM
authors.lastname: Chen
authors.forename: N L
authors.initials: NL
authors.lastname: Benoiton
mesh_terms: D000641:Ammonia; D003198:Computer Simulation; D005559:Formamides / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D007536:Isomerism; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D012984:Software; D013816:Thermodynamics; D014867:Water
chemical_list: D005559:Formamides; D007202:Indicators and Reagents; D010455:Peptides; D014867:Water; C031066:formamide; D000641:Ammonia; D005998:Glycine