Characterization of the Degradation Products of Luteinizing Hormone Releasing Hormone

Degradation Kinetics of Gonadorelin in Aqueous Solution

“…7,11,12 Linear regression using eq 1 with fixed pK a s at 5.8, 9.5, and 12 14 results in values for M 0 to M 4 similar to those in Table 3. For M 5 a value of (-1.8 ( 4.3) × 10 -42 was calculated.…”

“…7,11 In the pH range 4-6 solvent catalysis plays the most important role. Hydrolysis of the peptide bond on the amino site of the serine residue gives rise to P3, the heptapeptide Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 , and P4, the tripeptide pyroGlu-His-Trp.…”

“…Hydrolysis of the peptide bond on the amino site of the serine residue gives rise to P3, the heptapeptide Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 , and P4, the tripeptide pyroGlu-His-Trp. [6][7][8][9] Above pH 7 hydroxyl-catalyzed degradation emerges as the most important pathway, which results in products P1 and P2. P2 is probably the D-Ser 4 gonadorelin epimer, 7,11,12 and on the basis of the capacity factor and the m/z ratio, P1 is deamidated gonadorelin, the same as the degradation product of the proton-catalyzed reaction.…”

“…2 Limited research, however, was performed on the degradation of gonadorelin and its analogues. [3][4][5][6][7][8][9] Helm et al 3 investigated the kinetics of gonadorelin and triptorelin between pH 2 and 8, but the pH range was too small to characterize the different pH-dependent degradation reactions. The same holds for the gonadorelin study of Powell et al 4 and the nafarelin study of Johnson et al 5 Strickley et al 6 investigated systematically the degradation of RS-26306, a gonadorelin antagonist, and found that the degradation reactions can be divided into a proton-catalyzed deamidation, a solventcatalyzed hydrolysis, and a hydroxyl-catalyzed epimerization.…”

The Relative Rate of Immunoglobulin Gamma 1 Fragmentation

“…Compared with other relevant protein hydrolysis reactions, the E a for fragmentation is comparable; however, the expected E a would be lower, considering the presumed catalytic affect of Asp residues on fragmenation. [49][50][51][52] Similar E a of ∼91-93 kJ/mol have been determined from the effects of temperature on the deamidation and isomerization of Asn and Asp residues, respectively, in proteins and model peptides. [53][54][55][56][57] Fragmentation of the peptide backbone at Asp and Asn residues has been studied computationally with the interesting result that the activation barrier for backbone cleavage at Asp residues is much lower than at Asn.…”