title: Ester vs. amide on folding: a case study with a 2-residue synthetic peptide.
abstract: 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.
authors.affiliation: Division of Organic Chemistry, National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India. gj.sanjayan@ncl.res.in.
authors.forename: Kuruppanthara N
authors.initials: KN
authors.lastname: Vijayadas
authors.forename: Roshna V
authors.initials: RV
authors.lastname: Nair
authors.forename: Rupesh L
authors.initials: RL
authors.lastname: Gawade
authors.forename: Amol S
authors.initials: AS
authors.lastname: Kotmale
authors.forename: Panchami
authors.initials: P
authors.lastname: Prabhakaran
authors.forename: Rajesh G
authors.initials: RG
authors.lastname: Gonnade
authors.forename: Vedavadi G
authors.initials: VG
authors.lastname: Puranik
authors.forename: Pattuparambil R
authors.initials: PR
authors.lastname: Rajamohanan
authors.forename: Gangadhar J
authors.initials: GJ
authors.lastname: Sanjayan
mesh_terms: D000577:Amides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000577:Amides; D004952:Esters; D010455:Peptides