Peptides are short biopolymers naturally synthesized from a-amino acids, linked by an amide bond, also called a peptide bond. The features of a peptide structure or backbone, encompasses critical information about the backbone torsional angles y, and œ (Figure 8.1) were first investigated extensively by Ramachandran and coworkers, and % angles were carefully examined later.
The backbone torsional angles dictate the conformational space that is occupied by the peptide and are the most decisive feature of a bioactive peptide that exhibits affinity and biological activity toward receptors such as G protein-coupled receptors (GPCRs), proteases, or other proteins. In addition, side chain torsional angles (%) play crucial roles in protein-protein folding and peptide ligand-receptor interactions.
Synthetically designed a-helices, 0-sheets, 0-turns, and modifications of them, are important considerations for the design of a potent ligand/peptide. Mimicking or replacing atoms or bonds can introduce conformational constraints on the peptide structure, which can greatly affect the biological activity. Tuning such modifications forms the central theme for designing potent ligands for research and development and for designing peptide-based drugs.
Was this article helpful?