NMR Analysis of Aromatic Interactions in Designed Peptide β-Hairpins

Citations Over TimeTop 10% of 2006 papers

Abstract

Designed octapeptide beta-hairpins containing a central (D)Pro-Gly segment have been used as a scaffold to place the aromatic residues Tyr and Trp at various positions on the antiparallel beta-strands. Using a set of five peptide hairpins, aromatic interactions have been probed across antiparallel beta-sheets, in the non-hydrogen bonding position (Ac-L-Y-V-(D)P-G-L-Y/W-V-OMe: peptides 1 and 2), diagonally across the strands (Boc-Y/W-L-V-(D)P-G-W-L-V-OMe: peptides 3 and 6), and along the strands at positions i and i + 2 (Boc-L-L-V-(D)P-G-Y-L-W-OMe: peptide 4). Two peptides served as controls (Boc-L-L-V-(D)P-G-Y-W-V-OMe: peptide 5; Boc-L-Y-V-(D)P-G-L-L-V-OMe: peptide 7) for aromatic interactions. All studies have been carried out using solution NMR methods in CDCl(3) + 10% DMSO-d(6) and have been additionally examined in CD(3)OH for peptides 1 and 2. Inter-ring proton-proton nuclear Overhauser effects (NOEs) and upfield shifted aromatic proton resonances have provided firm evidence for specific aromatic interactions. Calculated NMR structures for peptides 1 and 2, containing aromatic pairs at facing non-hydrogen bonded positions, revealed that T-shaped arrangements of the interacting pairs of rings are favored, with ring current effects leading to extremely upfield chemical shifts and temperature dependences for specific aromatic protons. Anomalous far-UV CD spectra appeared to be a characteristic feature in peptides where the two aromatic residues are spatially proximal. The observation of the close approach of aromatic rings in organic solvents suggests that interactions of an electrostatic nature may be favored. This situation may be compared to the case of aqueous solutions, where clustering of aromatic residues is driven by solvophobic (hydrophobic) forces.

Related Papers

• → A universal scale of aromaticity for π‐organic compounds(2009)53 cited
• → σ‐Aromaticity in an Unsaturated Ring: Osmapentalene Derivatives Containing a Metallacyclopropene Unit(2015)44 cited
• → σ Aromaticity Dominates in the Unsaturated Three‐Membered Ring of Cyclopropametallapentalenes from Groups 7–9: A DFT Study(2015)41 cited
• → Adaptive σ‐Aromaticity in an Unsaturated Three‐Membered Ring(2020)21 cited
• → Are nucleus-independent (NICS) and 1H NMR chemical shifts good indicators of aromaticity in π-stacked polyfluorenes?(2006)34 cited