Although there is a need for antibacterial agents that act only on Gram-negative bacteria, there are at present few such compounds. The 2-deoxy analogue of beta-KDO (3-deoxy-beta-D-manno-2-octulopyranosonic acid) is a potent inhibitor of a key enzyme (CMP-KDO synthetase) in lipopolysaccharide biosynthesis of Gram-negative bacteria, but it fails to penetrate intact bacteria. Coupling an L-L-dipeptide to the 8-amino-2,8-dideoxy analogue of beta-KDO enabled it to be recognized and actively accumulated by certain peptide permeases of the cytoplasmic membrane. The dipeptide was hydrolysed in the cell and the inhibitor released. Subsequent inhibition of CMP-KDO synthetase led to the accumulation of large amounts of lipid A precursor and bacterial death. These compounds represent a new class of synthetic antimicrobials with a novel mechanism of action and considerable potential as chemotherapeutic agents.
Two related volatile compounds were identified from each of two species ofPissodes bark weevils and implicated as components of their aggregation pheromones. Grandisol (cis-2-isopropenyl-1-methylcyclobutaneethanol), and its corresponding aldehyde, grandisal, were isolated from males of bothP. strobi andP. approximatus and were found in the abdomens and hindguts of the respective species. In field tests synthetic grandisol and grandisal together with odors from cut pine acted synergistically in attracting both sexes ofP. approximatus. This response was similar to that elicited by maleP. approximatus feeding on cut pine. Males and females of natural populations ofP. strobi were more responsive to caged males feeding on leaders of white pine than they were to leaders alone. The combination of grandisol, grandisal, and leaders was less attractive than males on leaders, but more attractive than leaders alone. From isolation of pheromone components at different times of the year, it was determined that males of both species produced grandisol and grandisal only at times when cohort females were reproductively mature.
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