Conformational and aggregational states of omega-aminoacylmelittin derivatives.
Melittin, a 26-residue peptide from bee venom, is known to change from a largely random to a largely alpha-helical conformation as a function of peptide concentration, pH, and ionic strength. In this report, we have determined the effect of displacing the positive charges of the amino groups of N-terminal glycine and lysine residues away from the backbone of melittin in coil-to-helix transitions by using omega-aminoacyl derivatives of melittin. These were prepared by acylating the amino groups of melittin with omega-amino acids to yield the melittin derivatives glycylmelittin (MLT-2), (4-aminobutanoyl)melittin (MLT-4), and (5-aminopentanoyl)melittin (MLT-5), respectively. At pH 7.2, there is a chain-length-dependent increase in helicity from MLT to MLT-5. The omega-aminoacylmelittin derivatives also show a concentration-dependent increase in helicity at pH 7.2. However, at pH 2.3, a concentration-independent, but chain length-dependent increase in helicity was observed. A hydrophilic derivative glycylglycylmelittin (MLT-GG) and a hydrophobic derivative MLT-5, which have side chains of equal length, show similar helicity, at pH 7.2, but at pH 2.3 MLT-GG shows almost no helicity, while MLT-5 is about 60% helical. The lysyl derivative (MLT-K), which has additional positive charges compared to melittin, behaves much like MLT-2. At pH 7.2, all the derivatives exhibit both cold- and heat-induced denaturation; a significant amount of residual structure is retained in the temperature range 80-100 degrees C. These results are discussed in terms of the electrostatic and hydrophobic interactions involving the side chains.