Looking for the peptide 2.05-helix: A solvent- and main-chain length-dependent conformational switch probed by electron transfer across cα,α-diethylglycine homo-oligomers

The elusive, multiple fully extended (2.0(5)-helix) peptide conformation was searched with a series of C-alpha,C-alpha-diethylglycine homo-oligomers (n = 1 to 5) functionalized by an electron transfer (ET) donor center dot center dot center dot acceptor (D center dot center dot center dot A) pair in acetonitrile and chloroform solutions. In the former solvent, all peptides investigated were shown to populate the 3(10)-helix conformation, whereas in chloroform the two shortest members of the series (n = 1 and n = 2) adopt predominantly the 2.0(5)-helix. Interestingly, for the longest components (n = 3 to n = 5) in this latter solvent, an equilibrium between the 2.0(5)- and 3(10)-helices takes place, the latter conformation becoming progressively more populated as the peptide main-chain length increases. Time-resolved fluorescence (TRF) experiments and molecular mechanics (MM) calculations were used in a combined approach to analyze the ET efficiencies and to associate a specific conformer (from MM) to an experimentally determined ET rate constant (from TRF). Therefore, because of the high sensitivity of the ET process to the D center dot center dot center dot A distance, ET can be used as a kinetic spectroscopic ruler, allowing for the characterization of the transition from a pure 3(10)-helix conformation to a 2.0(5)-/3(10)-helix equilibrium for the longest Deg homo-peptides of this series upon changing the solvent from acetonitrile to chloroform. To our knowledge, this is the first time that the electronic coupling factor beta for ET across a peptide chain in the 2.0(5)-helix conformation is provided.