Figure 3. The structure of the peptoid sidechain affects triple-helical propensity.

a, T_m values for a series of X-CMPs with N-Cα-substituted 6-membered rings. There is little difference in triple-helical stability among the aliphatic, aromatic, and hydrophilic rings, and every peptide had a T_m higher than the host: Pro-CMP. b, Although charged groups destabilized the triple-helix at physiological pH, when the sidechains were uncharged, both Nlys and Nasp, as well as the hydrophilic Nasn, were as stabilizing as Pro. c, A series of X-CMPs with aliphatic sidechains of increasing size showing concomitantly increasing T_m values, implying an robust steric effect. Although the hydrophobicity in this series increases as the aliphatic sidechains increase in size, according to series a and b, hydrophobicity has only a minor effect on stability. The results suggest that the tertiary amide structure N-gly (which hinders the α helix and β sheet conformations) and the size of the N-substituted sidechain play the most critical roles in stabilization of N-gly-CMP triple-helices.