A His-Pro-Aib peptide that exhibits an Asx-Pro-turn-like structure

Area of Science:

• Peptide chemistry and structural biology.
• Conformational analysis of biomolecules.
• Structure-activity relationships in peptides.

Background:

• Small peptides are crucial in biological processes.
• Understanding peptide conformation is key to their function.
• N-terminal modifications can significantly alter peptide structures.

Purpose of the Study:

• To investigate the structural impact of different N-terminal residues on small peptides.
• To compare the solid-state and solution conformations of two related peptides.
• To elucidate the conformational preferences induced by BOC-Phe versus BOC-(tau-benzyl)His at the N-terminus.

Main Methods:

• X-ray crystallography for solid-state structure determination.
• Nuclear Magnetic Resonance (NMR) spectroscopy for solution structure analysis.
• Infrared (IR) spectroscopy to probe secondary structures in solution.

Main Results:

• Peptide 1, with an N-terminal BOC-Phe residue, consistently adopts a beta-turn conformation.
• Peptide 2, featuring an N-terminal BOC-(tau-benzyl)His residue, exhibits a distinct conformation resembling the Asx-Pro motif.
• Structural differences were observed in both solid and solution states, confirmed by X-ray, NMR, and IR data.

Conclusions:

• The N-terminal residue plays a critical role in dictating peptide secondary structure.
• A BOC-Phe residue favors beta-turn formation, whereas BOC-(tau-benzyl)His promotes an Asx-Pro-like conformation.
• These findings highlight the sensitivity of peptide structure to subtle sequence variations.