Direct Cleavage versus Transpeptidation in the Autodecomposition of Peptides Containing 2,4-Diaminobutanoic Acid (DABA) and 2,3-Diaminopropanoic Acid (DAPA) Residues. Specific Cleavage of DAPA-Containing Peptides

Article abstract of DOI:10.1021/ja00199a049

Peptides containing 2,4-diaminobutanoic acid and 2,3-diaminopropanoic acid residues undergo transpeptidation by attack of their side-chain amino groups on the N-carbonyl (eq. 2).Little or no direct cleavage by attack on the C-carbonyl (eq. 1) is observed.The transpeptidation reactions of peptides containing 2,4-diaminobutanoic acid (DABA) or 2,3-diaminopropanoic acid (DAPA) residues reach an equilibrium in which the various peptides studied are about 70-80percent transpeptidized; this extent of transpeptidation is in aggreement with the equilibrium constants for othertransamination reactions.The transpeptidation reaction is strongly catalyzed by phosphate and bicarbonate buffers, and the pH dependence of the reaction suggests that an unprotonated side-chain amino group is required for significant reactivity.The rate of the transpeptidation reaction is retarded by bulky substituents at the α-carbon of the residue at the amino-terminal side of the DAPA or DABA residue.The preference for transpeptidationdirect cleavage in the case of DABA residues can be explained by one or more of the following factors: (1) a preference for (Z)-amide (transpeptidation)(E)-amide (direct cleavage); (2) greater ring strain in the tetrahedral intermediate for direct cleavage; (3) a steric effect resulting from unfavorable interactions in the possible transition states for direct cleavage (Scheme III).A stereoelectronic explanation is considered and rejected.Peptides containing transpeptidized DABA and DAPA residues (isoDABA and isoDAPA residues, respectively) undergo cleavage at the carboxy-terminal side of these residues on treatment with the Edman reagent followed by treatment with trifluoroaceticacid.Peptides can be induced to undergo direct cleavage at the carboxy-terminal side of untranspeptidized DAPA residues by treatment with the Edman reagent followed by heptafluorobutyric acid.The chemical and biological significance of these observations is discussed.