Self-Association Behavior of aNovelNonproteinogenic β-Strand-Mimicin an Organic Solvent

Abstract

The self-association behavior of a newly characterized β-strand-mimic, presented by an achiral nonproteinogenic model system Boc-γ-Abz-NHMe (1: Boc = tert-butyloxycarbonyl; γ-Abz = γ-aminobenzoic acid; NHMe = N-methylamide), have been investigated using 1H NMR and FT-IR absorption spectroscopy, in combination with computational ab initio calculations. The concentration dependence of 1H NMR chemical shifts of the amide-NHs in CDCl3 exhibited noncooperative behavior of self-association, whereas the variable temperature 1H NMR chemical shifts data of the amide-NHs, i.e., temperature-coefficient (Δδ/ΔT) values, could be accounted for by significant enhancement of self-association, i.e., aggregates higher than dimers. In the absence of N–H···O intramolecular H-bond in 1, the intense FT-IR absorption bands in informative amide-A region, i.e., N–H stretches at ∼3465 and 3438 cm–1 in chloroform solution, could be interpreted in terms of intermolecular H-bonding. The ab initio quantum mechanical calculations performed on two discrete isolated antiparallel H-bonded duplexes with a face-to-face and an edge-to-edge aromatic–aromatic interaction provided strong support for their relative importance to stabilize favorable dimeric structures. The thermodynamic parameters deduced from van’t Hoff plots, constructed from variable temperature 1H NMR data of the amide-NHs in CDCl3, also substantiated the effectiveness of aromatic–aromatic interactions for dimer formation and higher-order self-association. In view of the enormous structural importance of β-strand-like building blocks in peptide design, we highlight intrinsic self-associating potentials of the readily available γ-Abz moiety, besides the fact that such planar secondary structural mimics are presumed to offer greater prospective for constructing peptidomimetics and therapeutically relevant small molecules.