No abstract

No abstract

No abstract

No abstract

The cyclic polypeptide alamethicin, when incorporated into a lipid bilayer imparts ion-gating properties resembling the electrical characteristics of natural membranes more closely than any other synthetic system. A model is described in which the molecule assumes a disc-like conformation, with the cyclic polypeptide structure extending around the circumference [l] . Physical studies [2,3] indicate a high lipid solubility, and specific interaction with phospholipids in artificial systems. Following the determination of the amino acid sequence of alamethicin, the model has been modified to accommodate this and also the previously undetected cyclising y-linked side chain, -Glu-Gln. The presumed ion binding groups have been located at the centre, in the form of a molecular pore [4]. We have examined the conformational properties of alamethicin in a variety of solvents by ORD and CD. The spectroscopic results indicate that the molecule assumes a compact conformation in hydrophobic environments. We propose that this conformation, which may contain up to 40% helical structure, is significant in the action of alamethicin on bilayer membranes.The ORD and CD spectra are strongly solvent sensitive, showing greater amplitude with increasing hydrophobicity of the solvent. Fig. 1 shows the increase (more than 2-fold) in the negative troughs in CD at 207 nm and 220 nm on going from 10% ethanol in water to 100% ethanol. Similar effects have been found for methanol, dioxane and acetonitrile. Intensification of this spectrum is found in the presence of 278 detergents such as 1% sodium dodecyl sulphate ( fig. l), 1% sarkosyl and 5% sodium deoxycholate, though in these cases the 207 nm trough is less pronounced.