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Acid-catalyzed hydrolysis of peptide-amides in the solid state
P B Ten Kortenaar1, B M Hendrix, J W Van Nispen
1Organon Scientific Development Group, Oss, The Netherlands.
International Journal of Peptide and Protein Research
|September 1, 1990
Summary
Residual strong acids rapidly hydrolyze peptide-amides in solid states, even at 4°C. Steric hindrance from bulky C-terminal residues significantly protects peptide amides from this acid-catalyzed deamidation.
Area of Science:
- Solid-state chemistry
- Peptide chemistry
- Acid catalysis
Background:
- Peptide-amide bonds are susceptible to hydrolysis.
- Understanding degradation pathways is crucial for peptide stability.
- Solid-state reactions require specific investigation due to different kinetics.
Purpose of the Study:
- To investigate the solid-state hydrolysis of peptide-amides.
- To determine the effect of residual strong acids on peptide-amide stability at low temperatures.
- To identify factors influencing the rate and extent of deamidation.
Main Methods:
- Experimental investigation of peptide-amide hydrolysis in the solid state.
- Controlled exposure to residual strong acids at 4°C.
- Analysis of deamidation extent based on acid properties (pKa, volatility) and peptide structure.
Main Results:
- Small molar excesses of strong acids cause substantial deamidation within 24 hours, even at 4°C.
- Acid pKa and volatility influence hydrolysis rates.
- Steric accessibility of the amide group is a critical factor; bulky C-terminal residues confer greater stability.
Conclusions:
- Solid-state peptide-amides are highly susceptible to hydrolysis by residual strong acids at low temperatures.
- Acid characteristics and steric factors dictate the degree of deamidation.
- Peptide sequence and conformation play a significant role in solid-state stability against acid-catalyzed degradation.