title: Synthesis and biological evaluation of analogues of the antibiotic pantocin B.
abstract: Strains of the bacteria Erwinia herbicola produce antibiotics that effectively control E. amylovora, the bacterial pathogen responsible for the plant disease fire blight. Pantocin B was the first of these antibiotics to be characterized, and a flexible synthesis of various analogues is reported. Embedded in the "pseudo-tripeptide" backbone of pantocin B are a methylenediamine and a methyl sulfone, both unusual structural features in natural products. The peptidic nature of pantocin B facilitated a series of structure-activity relationship studies that probed the roles of these functional groups 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 interaction with the intracellular target, the arginine biosynthetic enzyme N-acetylornithine aminotransferase. The methylenediamine and methyl sulfone portions were found to be essential for antibiotic activity, presumably due to extensive interactions with N-acetylornithine aminotransferase.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Sutton
authors.forename: J
authors.initials: J
authors.lastname: Clardy
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004885:Erwinia / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008293:Malates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D008293:Malates; C410984:pantocin B; D005998:Glycine