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Deamidation via cyclic imide in asparaginyl peptides
S Capasso1, L Mazzarella, F Sica
1Dipartimento di Chimica, Università di Napoli, Italy.
Peptide Research
|March 1, 1989
Summary
Asparagine deamidation and aminosuccinyl peptide hydrolysis accelerate at higher pH. The peptide sequence influences these reactions, forming succinimide intermediates and leading to normal and isoaspartyl peptides.
Area of Science:
- Biochemistry
- Chemical Kinetics
- Peptide Chemistry
Background:
- Asparagine deamidation is a common post-translational modification.
- This reaction can lead to the formation of isoaspartyl residues, potentially affecting protein function.
- Understanding the kinetics and sequence dependence is crucial for predicting peptide and protein stability.
Purpose of the Study:
- To investigate the deamidation of asparaginyl peptides.
- To study the hydrolysis of aminosuccinyl (Asu) peptides.
- To determine the influence of pH and neighboring amino acid residues on these reactions.
Main Methods:
- Studied deamidation of Boc-Asn-Gly-Gly-NH2 and Boc-Asu-Gly-Gly-NH2 across pH 5-10.
- Examined deamidation of Boc-Asn-Ala-Gly-NH2, Boc-Asn-Gly-Ala-NH2, and Boc-Asn-Ser-Gly-NH2 at pH 8.9.
- Analyzed reaction kinetics, including succinimide intermediate formation and breakdown.
Main Results:
- Deamidation and Asu hydrolysis rates increase significantly at basic pH.
- The reaction proceeds via a succinimide (Asu) intermediate.
- The side chain of the residue adjacent to asparagine influences the reaction rate.
Conclusions:
- Asparagine deamidation and subsequent hydrolysis are pH-dependent, accelerating under alkaline conditions.
- The formation of normal and isoaspartyl peptides is a consequence of succinimide intermediate breakdown.
- Neighboring amino acid residues play a role in modulating the kinetics of asparagine modification.