Conformation and chiral effects in α,β,α-tripeptides

Area of Science:

• Peptide Chemistry
• Structural Biology
• Organic Chemistry

Background:

• Short peptides can adopt various secondary structures.
• Chiral amino acids play a crucial role in determining peptide conformation.
• The influence of central β-amino acids on tripeptide turns is not fully understood.

Purpose of the Study:

• To investigate the conformational preferences of short α,β,α-tripeptides containing a central chiral trisubstituted β-amino acid.
• To elucidate the impact of the central β-amino acid's configuration on peptide secondary structure formation.
• To compare solution-state conformations with crystal structures.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy (2D-NMR).
• Analysis of thermal coefficients of backbone amide protons.
• Molecular modeling and simulation.
• X-ray crystallography.

Main Results:

• Tripeptides formed unusual γ-turns and δ-turns, but not β-turns.
• Conformations were highly dependent on the stereochemical configuration of the central β-amino acid.
• SSS tripeptides adopted a γ-turn like (C6) arrangement.
• SRS diastereomers favored an extended δ-turn (C9) in solution.
• Crystal structures of SRS compounds showed an extended δ-turn (C9) with an additional β-turn (C11), forming a double turn motif.

Conclusions:

• The central chiral β-amino acid is a key determinant of short tripeptide secondary structure.
• Distinct conformational preferences (γ-turn vs. δ-turn) arise from different stereochemical configurations.
• A combination of solution and solid-state studies reveals complex, overlapped turn motifs in SRS tripeptides.