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In recent years there has been a resurgence of interest in melittin and its variants as their therapeutic potential has become increasingly evident. Melittin is a 26-residue peptide and a… Click to show full abstract
In recent years there has been a resurgence of interest in melittin and its variants as their therapeutic potential has become increasingly evident. Melittin is a 26-residue peptide and a toxic component of honey bee venom. The versatility of melittin in interacting with various biological substrates, such as membranes, glycosaminoglycans and a variety of proteins has inspired a slew of studies to understand the structural basis of such interactions. However, these studies have largely focused on melittin solutions at high concentrations (> 1mM), even though melittin is generally effective at lower, (micromolar) concentrations. Here we present high-resolution NMR studies in the lower concentration regime using a novel method to produce isotope labeled (15N, 13C) recombinant melittin. We provide residue-specific structural characterization of melittin in dilute aqueous solution and in TFE-water mixtures, which mimic melittin structure-function and interactions in aqueous, and membrane-like environments res...