Ester vs. amide on folding: a case study with a 2-residue synthetic peptideElectronic supplementary information (ESI) available: 1H, 13C, DEPT-135 NMR, 2D study spectra, ESI mass spectra and theoretical study of new compounds are included. CCDC 874039, 699500, 874040, 874041, 874042, 874043, 679454, 874044, 874045, 874046 and 874047. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ob41967c

Although known for their inferiority as hydrogen-bonding acceptors when compared to amides, esters are often found at the C-terminus of peptides and synthetic oligomers (foldamers), presumably due to the synthetic readiness with which they are obtained using protected peptide coupling, deploying amino acid esters at the C-terminus. When the H-bonding interactions deviate from regularity at the termini, peptide chains tend to "fray apart". However, the individual contributions of C-terminal esters in causing peptide chain end-fraying goes often unnoticed, particularly due to diverse competing effects emanating from large peptide chains. Herein, we describe a striking case of a comparison of the individual contributions of C-terminal ester vs. amide carbonyl as a H-bonding acceptor in the folding of a peptide. A simple two-residue peptide fold has been used as a testing case to demonstrate that amide carbonyl is far superior to ester carbonyl in promoting peptide folding, alienating end-fraying. This finding would have a bearing on the fundamental understanding of the individual contributions of stabilizing/destabilizing non-covalent interactions in peptide folding. This article unveils a striking case of comparison of the individual contributions of C-terminal ester vs. amide carbonyl as a H-bonding acceptor in the folding of a synthetic peptide.