The -BF-NH- link as a peptide-bond surrogate

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Medicinal Chemistry

Background:

• Peptidomimetics are crucial for developing new therapeutics and understanding biological processes.
• Modifying the peptide backbone offers a route to novel molecular structures with altered properties.
• The amide linkage is a fundamental component of peptides, influencing their structure and function.

Purpose of the Study:

• To investigate the theoretical effects of substituting the amide carbonyl group (C═O) with a boron-fluorine (B-F) bond.
• To compare the properties of a novel fluoro-aminoborane peptidomimetic with natural N-methylacetamide.
• To analyze the impact of this substitution on polarity, hydrogen bonding, and conformational behavior.

Main Methods:

• Comparative theoretical calculations were performed on dimethyl-fluoro-aminoborane and N-methylacetamide models.
• Analysis included electronic structure, size, rigidity, polarity, and association energies.
• Conformational maps of corresponding dipeptide models were generated and analyzed.

Main Results:

• Minimal differences were observed in size, electronic structure, and rigidity between the B-F and C═O models.
• Substantial distinctions were found in polarity and association energies, with B-F···H-N hydrogen bonds being weaker than C═O···H-N.
• Fluoro-aminoborane dipeptide models showed similarities and differences in conformational maps, affecting helical oligomer properties.

Conclusions:

• The B-F substitution in the amide linkage creates a peptidomimetic with distinct polarity and hydrogen bonding characteristics.
• Chains composed of fluoro-aminoborane units exhibit less structuration and greater plasticity than natural peptide chains.
• This novel peptidomimetic approach offers potential for designing molecules with tailored structural and functional properties.