Showing papers by "Richard M. Epand published in 1988"

Modulation of the bilayer to hexagonal phase transition and solvation of phosphatidylethanolamines in aqueous salt solutions.

Abstract: Several salts affect the temperature of the bilayer to hexagonal phase transition of phosphatidylethanolamines. Their effects are dependent on the anion as well as the cation of the salt. Salt effects on this transition can be explained by preferential hydration and ion binding. Those salts which are excluded from the solvation sphere of the membrane promote hexagonal phase formation. For example, Na2SO4 promotes preferential hydration and is a hexagonal phase promoter while NaSCN does not do this and is a bilayer stabilizer. Unlike amphiphiles and hydrocarbons, salts can shift the bilayer to hexagonal phase transition temperature without altering the cooperativity of the transition. The effect of these salts on the gel to liquid-crystal transition is opposite to their effect on the bilayer to hexagonal phase transition. We also find that MnCl2 markedly raises the gel to liquid-crystal transition temperature. This effect is due to binding of the cation to the membrane surface. The effect is reduced with MnSO4 because of preferential hydration. Our results demonstrate that the nature of the anion as well as the cation can alter the effect of salts on lipid phase transition properties. The observed effects can be explained as resulting from preferential hydration and ion binding.

The relationship between the bilayer to hexagonal phase transition temperature in membranes and protein kinase C activity.

Abstract: A number of substances affect the activity of protein kinase C. Among uncharged and zwitterionic compounds, those which activate protein kinase C also lower the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine while substances which inhibit protein kinase C raise this transition temperature. Using this criteria, we have identified 3β-chloro-5-cholestene, 5β-cholan-24-ol and eicosane as new protein kinase C activators and have shown that Z-Ser-Leu-NH2, Z-Gly-Leu-NH2, Z-Tyr-Leu-NH2, cyclosporin A and cholestan-3β, 5α, 6β-triol are protein kinase C inhibitors.

Deletion sequences of salmon calcitonin that retain the essential biological and conformational features of the intact molecule.

Abstract: Salmon calcitonin has an amino acid sequences that would allow it to form an amphipathic helix from approximately residue 9 to residue 22. We have synthesized a number of analogues of this peptide hormone with deletions in the carboxyl terminus of this putative amphipathic helix. These analogues include deletions of single amino acid residues at positions 19, 20, 21, or 22 as well as deletions of progressively larger segments starting with residue 19 and including deletions of residues 19 and 20; 19, 20, and 21; or 19, 20, 21, and 22. There is a small decrease in the helical content of these analogues compared with the native hormone, both in the presence and absence of amphiphiles. However, the extent of formation of secondary structure, as measured by circular dichroism, is similar for these deletion sequences as it is for the native hormone. In all cases, there is a large increase in the helical content of the peptide in the presence of dimyristoylphosphatidylglycerol, lysolecithin, or sodium dodecyl sulfate. All of the analogues have hypocalcemic activity in vivo in rats, comparable to the native hormone, except for des-Leu19-salmon calcitonin, which is about twice as active as the unmodified hormone. With use of an in vitro assay of adenylate cyclase activation in purified rat kidney membranes, des-Tyr22-salmon calcitonin, des-Leu19,Gln20,Thr21-salmon calcitonin, and des-Leu19Gln20,Thr21,Thr22-salmon calcitonin exhibited about one-tenth the stimulatory activity of the native hormone. Des-Tyr22-sCT and des-Leu19,Gln20,Thr21,Tyr22-sCT were also tested for their activity in inhibiting prolactin release from isolated rat pituitary cells. Both of these analogues exhibited inhibitory activity. Thus, the region of residues 19-22 does not greatly affect either the conformational or the biological properties of salmon calcitonin.