Synthesis of analogs of K-582A, an antibiotic heptapeptide

K-582 A, an antibiotic heptapeptide, has a sequence of H-L-Arg-L-Arg(OH)-D-Orn-L-Thr-D-Orn-L-Lys-D-Tyr-OH (Arg(OH), threo-gamma-hydroxyarginine). In order to investigate the relationship between structure and antimicrobial activity, four shortened analogs, des-L-Arg1, L-Arg(OH)2-K582 A (pentapeptide), des-L-Arg(OH)2-K-582 A (hexapeptide) and their N-acetyl derivatives, were synthesized by the conventional method. None of them, however, showed any antimicrobial activity. Three more analogs, [L-Lys2]K-582 A, [L-Orn2]K-582 A and [L-Arg2]K-582 A, were synthesized. Among them, only [L-Arg2]K-582 A showed substantial activity against Candida krusei and Saccharomyces rouxii, indicating that the presence of a guanidyl side chain at position 2 is an essential factor for the induction of activity.