Melittin, a 26-residue peptide from bee venom, is transformed from a largely random to a largely alpha-helical conformation at elevated pH. At 3 x 10(-5) M melittin, circular dichroism spectra show a transition with a pK near 9.6. At 8 x 10(-5) M, two approximately equal transitions occur with pKs at 7.2 and 9.6. At 6 x 10(-4) M, a single transition is seen with a pK of 6.8, followed by a more gradual increase to at least pH 11. The transitions near pH 7 presumably arise from deprotonation of the alpha-amino group. When the amino groups are acetylated or succinylated, a 60% alpha-helical conformation is adopted at neutral or low pH. The acylated melittins form more stable oligomers than does native melittin.

The interactions of N-methylacetamide (NMA) and N,N-dimethylacetamide (DMA) with denaturants were studied by viscometry, calorimetry, and crystallography. Lithium and calcium chlorides show strong interactions by all three criteria; these cations probably interact with peptide groups.Alkali thiocyanate, nitrate, and perchlorate salts show T here are two general mechanisms by which salts may denature proteins: (1) interaction with the protein, probably at peptide or other polar groups (possibly including the ir electrons of the aromatic side chains);(2) alteration of the solvent structure. We shall not consider here salts with large apolar chains which can be bound to apolar regions of the protein. Geschwind (1960) reported that aqueous mixtures of urea and lithium bromide showed high viscosities; similar viscosity increases were found by Bello and Bello (1961,1962) for aqueous solutions of lithium chloride or bromide with N-methylacetamide (NMA)' or N,N-dimethylacetamide (DMA). DMA was investigated as an analog of proline and hydroxyproline which contain no NH group when present in peptide linkage. These observations led to the suggestion that lithium halides interact with the amide groups, and that they denature proteins by interaction with peptide or other polar groups. Crystalline complexes of NMA with lithium chloride and bromide were obtained (Bello and Bello, 1962) from an aqueous environment and their structures have been determined by X-ray diffraction (Haas, 1964). In these complexes there are carbonyl-lithium interactions and "-halide hydrogen bonds. In this communication, we report viscometric, calorimetric, and crystallographic data on the interactions of NMA and DMA with a number of denaturing salts.

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