Ester vs. amide on folding: a case study with a 2-residue synthetic peptide

TitleEster vs. amide on folding: a case study with a 2-residue synthetic peptide
Publication TypeJournal Article
Year of Publication2013
AuthorsVijayadas, KN, Nair, RV, Gawade, RL, Kotmale, AS, Prabhakaran, P, Gonnade, RG, Puranik, VG, Rajamohanan, PR, Sanjayan, GJ
JournalOrganic & Biomolecular Chemistry
Date PublishedDEC

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.

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Divison category: 
Center for Material Characterization (CMC)
Central NMR Facility
Organic Chemistry