Synthesis and biological evaluation of analogues of the antibiotic pantocin B

Strains of the bacteria Erwinia herbicola produce antibiotics that effectiv ely control E. amylovora, the bacterial pathogen responsible for the plant disease fire blight. Pantocin B was the first of these antibiotics to be ch aracterized, and a flexible synthesis of various analogues is reported. Emb edded in the "pseudo-tripeptide" backbone of pantocin B are a methylenediam ine and a methyl sulfone, both unusual structural features in natural produ cts. The peptidic nature of pantocin B facilitated a series of structure-ac tivity relationship studies that probed the roles of these functional group s in determining,the biological activity of pantocin B. A clear demarcation of the roles between the N- and C-terminal portions of the antibiotic. was determined as a result of the structure-activity relationship studies. The N-terminal L-alanyl group is needed for cellular import but not for intera ction with the intracellular target, the arginine biosynthetic enzyme N-ace tylornithine aminotransferase. The methylenediamine and methyl sulfone port ions were found to be essential for antibiotic activity, presumably due to extensive interactions with N-acetylornithine aminotransferase.