Linear peptide Product Ring size Yield (%) As previously mentioned, macrocycle embedded oxadiazole-grafts have historically proven to be unique and effective structural control in peptide macrocycles. A predictable and invariable beta-turn stabilizing effect can be observed in most oxdiazole-grafted macrocycles. In 2018, our group showed that a hydrogen bond between the endocyclic amine and the amide proton of the subsequent amino acid residue is common to every peptide of this group that has been made thus far. Given this, we were keen to examine the degree to which the peptide backbone could be modulated using the structurally diverse and synthetically accessible heterobiaryl-grafted peptide macrocycles of Table . We suspected that both alteration of the heterobiaryl f-angle as well as the substitution pattern of the heterobiaryl linkage would lead to measurable downstream structural effects. To determine the conformation of each macrocycle, conformational searches were performed using restraints from NOE-derived interproton distances, and backbone dihedral angles extracted from the NH/α-proton scalar coupling constants in d6-DMSO to generate crude structures. These structures were then subjected to 100 ns of solvent explicit molecular dynamics (OPLS4) simulations, and the resulting trajectory was clustered to determine the most populated conformers. The conformer that best matched the NOE distance restraints was deemed the preferred solution structure. Variable-temperature 1 H NMR analysis was also utilized to evaluate intramolecular hydrogen bonding (IMHB) networks between specific amide residues. Typically, temperature coefficients of greater than -4 ppb/K indicate that an amide NH is non-solvent exposed or involved in IMHB.