NCα-gem-dimethylated peptoid side chains: A novel approach for structural control and peptide sequence mimetics

Area of Science:

• Synthetic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Designing peptoid oligomers with defined secondary structures is crucial for drug discovery.
• Existing cis-inducing peptoid side chains have limited efficiency and chemical diversity.

Purpose of the Study:

• To introduce novel NCα-gem-dimethylated peptoid residues that mimic proteinogenic amino acids.
• To explore synthetic strategies for incorporating these residues into peptoid heterooligomers.
• To investigate the conformational control exerted by these new residues.

Main Methods:

• Submonomer synthesis and block-coupling approaches were used.
• NMR spectroscopy was employed to study monomer and trimer models.
• Molecular modeling was performed to analyze substituent orientation.

Main Results:

• A new array of NCα-gem-dimethylated peptoid residues was synthesized.
• These residues demonstrated complete cis control over backbone amide conformation.
• Preliminary molecular modeling provided insights into side chain orientation.

Conclusions:

• NCα-gem-dimethylated peptoid residues offer a promising strategy for controlling secondary structure in peptoid oligomers.
• This work expands the chemical diversity and synthetic accessibility of peptoids for applications in drug discovery.