The Peptide Bond

The peptide bond is the defining linkage of proteins. Its formation, catalyzed by the ribosome during translation, is an endergonic process requiring energy. The bond itself has a planar geometry due to resonance, which restricts the rotation around the C-N bond, giving it partial double-bond character. This planarity is crucial for the predictable folding patterns of polypeptide chains into secondary structures like alpha-helices and beta-sheets. The bond angles, specifically the phi (\(\phi\)) and psi (\(\psi\)) torsion angles of the polypeptide backbone, are constrained, as described by the Ramachandran plot. While the peptide bond is kinetically stable, it can be hydrolyzed (broken) by the addition of water, a process catalyzed by enzymes called proteases or by strong acids/bases. Understanding its chemical properties was a foundational step in biochemistry, moving the field from studying crude ‘albumins’ to understanding proteins as defined polymers with specific sequences and structures.

Historically, the nature of the linkage between amino acids was a major debate. Emil Fischer’s work on synthesizing small peptides and showing they behaved like natural protein fragments provided strong evidence for the peptide bond theory, which he and Franz Hofmeister proposed at the same conference in 1902. This discovery was revolutionary, establishing the polymer nature of proteins and paving the way for sequencing, synthesis, and structural biology.