The preferred solid-state conformation of (alpha Me)Trp peptides

Area of Science:

• Peptide Chemistry
• Structural Biology
• Organic Synthesis

Background:

• Diastereomeric dipeptides are crucial for understanding peptide conformation.
• Alpha-methylation of amino acid residues can significantly alter peptide structures and properties.
• Tryptophan derivatives are important in peptide design due to their unique electronic and steric properties.

Purpose of the Study:

• To synthesize and characterize Z-L-Ala-DL-(alpha Me)Trp-NH2 diastereomeric dipeptides.
• To determine the molecular and crystal structure of Z-L-Ala-L-(alpha Me)Trp-NH2 using X-ray diffraction.
• To investigate the conformational preferences and implications of the C alpha-methylated Tryptophan residue in peptide structures.

Main Methods:

• Synthesis of diastereomeric dipeptides via phase-transfer catalysis and hydrolysis.
• Separation of diastereomers using silica-gel column chromatography.
• X-ray diffraction analysis for molecular and crystal structure determination.

Main Results:

• Both molecules of Z-L-Ala-L-(alpha Me)Trp-NH2 adopted a type-II beta-bend conformation.
• Intramolecular hydrogen bonding stabilized the beta-bend in molecule B.
• The C alpha-methylated Tryptophan residue was identified as a strong beta-bend and helix former.
• Chirality of (alpha Me)Trp showed an inverse relationship with helix screw sense compared to protein amino acids.

Conclusions:

• The C alpha-methylated Tryptophan residue is a potent inducer of beta-bends and helices.
• The stereochemical outcome of helix formation involving (alpha Me)Trp differs from that of natural amino acids.
• These findings have implications for designing conformationally restricted peptide analogs with specific biological activities.