Structural chemistry and membrane modifying activity of the fungal polypeptides zervamicins, antiamoebins and efrapeptins
The fungal polypeptides zervamicins, antiamoebins and efrapeptins have been fractionated into several polypeptide components by HPLC. A zervamicin fraction lacking tryptophan has been characterized and shown to possess an N-terminal leucine residue. The conformations of zervamicin IIA and a synthetic analog in solution are compared with those determined for the related peptide, antiamoebin. The results are consistent with a completely helical structure for the apolar analog of zervamicin in chloroform, with partial unfolding in dimethylsulfoxide. A similar conformation has been determined for natural zervamicin IIB. A synthetic analog of efrapeptin forms a continuous helix in apolar solvents while, partial unfolding is seen in polar solvents. Natural zervamicin is an effective uncoupler of mitochondrial oxidative phosphorylation. Significant differences in membrane modifying activity are noted for the natural peptide and the synthetic apolar analog of zervamicin.