Norton P. Peet

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Murine macrophage-derived tumor necrosis factor alpha (TNF-alpha) gene expression has been shown to be dramatically induced by bacterial lipopolysaccharide, and to be dependent upon nuclear factor-kappa B (NF-kappa B) binding sites in its promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells were found to predominantly express the(More)
The structurally related neuropeptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), which belong to a family of molecules termed tachykinins and are widely distributed in the central and peripheral nervous systems, influence the function of many tissues. SP and NKA have links to the following chronic diseases: asthma, inflammatory bowel(More)
Given the limited number of structural classes of clinically available antimicrobial drugs, the discovery of antibacterials with novel chemical scaffolds is an important strategy in the development of effective therapeutics for both naturally occurring and engineered resistant strains of pathogenic bacteria. In this study, several diarylamidine derivatives(More)
Antimicrobial susceptibilities of 233 gram-positive and 180 gram-negative strains to two novel bis-indoles were evaluated. Both compounds were potent inhibitors of gram-positive bacteria, with MIC(90) values of 0.004 to 0.5 microg/ml. One bis-indole, MBX 1162, exhibited potent activity against all gram-negative strains, with MIC(90) values of 0.12 to 4(More)
NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogues have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of(More)
We have recently shown that alpha-MAPI, a peptidic aldehyde of microbial origin, inhibits the HIV protease with a potency comparable to pepstatin, having, differently from pepstatin, no activity on other aspartic proteases. In this study different peptide derivatives containing a C-terminal aldehyde have been tested to assess the potential of this function(More)
Botulinum neurotoxins (BoNTs) are the most lethal of biological substances, and are categorized as class A biothreat agents by the Centers for Disease Control and Prevention. There are currently no drugs to treat the deadly flaccid paralysis resulting from BoNT intoxication. Among the seven BoNT serotypes, the development of therapeutics to counter BoNT/A(More)
Many genetic (gene deletion, interruption or mutation), epigenetic (such as antisense or small interfering RNA) and immunological methods are being applied in 'high-throughput target validation' studies of the novel potential targets arising from whole genome sequencing. Such applications often focus on 'loss of function' approaches. However, target(More)
The increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. Previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. Here we report the synthesis and evaluation of optimized(More)
The type III secretion system (T3SS) is a clinically important virulence mechanism in Pseudomonas aeruginosa that secretes and translocates up to four protein toxin effectors into human cells, facilitating the establishment and dissemination of infections. To discover inhibitors of this important virulence mechanism, we developed two cellular reporter(More)