XII. Conformational studies of histidine-containing peptides in solution

Area of Science:

• Biophysical Chemistry
• Structural Biology
• Peptide Chemistry

Background:

• Understanding peptide conformation is crucial for biological function.
• Histidine-containing peptides exhibit complex conformational behaviors influenced by ionization states.

Purpose of the Study:

• To investigate the conformational equilibria of histidine, glycylhistidine, histidylglycine, and glycylhistidylglycine.
• To evaluate the impact of ionization on side-chain rotamer distribution and overall molecular conformation.
• To determine thermodynamic parameters governing conformational changes.

Main Methods:

• UV-Vis spectroscopy
• Circular Dichroism (CD) spectroscopy
• Nuclear Magnetic Resonance (NMR) spectroscopy (proton NMR)
• Variable temperature studies (200-320 K)
• Analysis of different ionic forms
• Correlation of NMR and CD data
• Theoretical energy calculations

Main Results:

• Ionization state significantly influences histidyl side-chain rotamer distribution and overall molecular conformation.
• Thermodynamic parameters (ΔH°, ΔS°) for side-chain conformational equilibrium were evaluated.
• Significant entropy differences between rotamers were observed in some cases.
• Conformer ellipticities were estimated for histidine and histidylglycine in basic solution.
• Convergence of experimental (NMR, CD) and theoretical data identified stable solution conformations.

Conclusions:

• The study elucidates the intricate relationship between ionization state and peptide conformation.
• NMR and CD spectroscopy provide complementary insights into molecular structure and dynamics.
• Thermodynamic analysis quantifies the stability of different peptide conformers in solution.