Structural chemistry and membrane modifying activity of the fungal polypeptides zervamicins, antiamoebins and efrapeptins

Abstract

The fungal polypeptides zervamicins, antiamoebins and efra-peptins 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 phos-phorylation. Significant differences in membrane modifying activity are noted for the natural peptide and the synthetic apolar analog of zervamicin. © 1990 IUPAC