Acid catalysis in the formation of dioxopiperazines from peptides containing tetrahydroisoquinoline-3-carboxylic acid at position 2.
The kinetics of the spontaneous formation of 2,5-dioxopiperazines from peptides containing the Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) residue in the 2-position of the sequence has been studied in DMSO and water solution. The reaction is first order in Tic-peptide and subject to general-acid catalysis. Moreover, only the fraction of peptide having the amino terminal group in the deprotonated state reacts with appreciable rate. In pure organic solvent, and in aqueous solution with low buffer concentration, the degradation reaction of Tic-peptides is very low; at 20 degrees C for the peptide H-Tyr-Tic-Phe-Phe-NH2, in DMSO and in neutral water in the absence of buffer, the half-lives (t1/2) are 3 x 10(4) and 1.2 x 10(4) h, respectively. The addition of carboxylic acids or buffers to the reaction solutions markedly increases the reaction rate; in 0.01 m HAc in DMSO and in 0.1 M phosphate buffer in water, pH 7.1, t1/2 values for the tetrapeptide are 61 and 121 h, respectively.
Capasso
S
S
Department of Chemistry, University of Naples Federico II, Italy.
Sica
F
F
Mazzarella
L
L
Balboni
G
G
Guerrini
R
R
Salvadori
S
S
D000143:Acids; D000595:Amino Acid Sequence; D002021:Buffers; D002384:Catalysis; D054659:Diketopiperazines; D004121:Dimethyl Sulfoxide; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000032:analysis*; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis*; D044005:Tetrahydroisoquinolines; D014867:Water
D000143:Acids; D002021:Buffers; D054659:Diketopiperazines; D007546:Isoquinolines; D010455:Peptides; D010879:Piperazines; D044005:Tetrahydroisoquinolines; D014867:Water; C010939:2,5-dioxopiperazine; C078986:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D004121:Dimethyl Sulfoxide