Karen L. Hulme

Bio: Karen L. Hulme is an academic researcher. The author has contributed to research in topics: Benzyl bromide & Lactobacillus plantarum. The author has an hindex of 3, co-authored 8 publications receiving 59 citations.

Synthesis and antibacterial activities of some chloro analogs of 3 amino-3,4-dihydro-1-hydroxycarbostyril.

Abstract: The effects of a chloro substituent upon the microbiological activities of 3-amino-3,4-dihydro-1-hydroxycarbostyril were determined. The 5-, 6-, and 7-chloro analogs were synthesized by reductive cyclizations of the appropriately chloro-substituted o-nitrophenylalanines, while the 8-chloro analog was obtained from the N-trifluoroacetyl-3-chloro-2-nitrophenylalanine ethyl ester. All of these compounds were observed to inhibit the growth of Escherichia coli 9723, Leuconostoc dextranicum 8086, and Lactobacillus plantarum 8014. The relative inhibitory activities of the chloro analogs were 7-Cl greater than 6-Cl greater than 8-Cl greater than 5-Cl in E. coli and 7-Cl greater than 6-Cl greater than 8-Cl = 5-Cl in L. dextranicum and L. plantarum. In each of the three microorganisms, the 7-Cl analog was a more effective growth inhibitor than the parent unsubstituted compound. The growth inhibitory activities of this class of compounds were demonstrated to be much more effective than those of the four corresponding lactams, the 5-, 6-, 7-, and 8-chloro analogs of 3-amino-3,4-dihydrocarbostyril.

Synthesis and microbiological activities of some monohalogenated analogs of tyrosine

Abstract: 2-Chlorotyrosine and 2-bromotyrosine, as well as the previously reported 2-fluorotyrosine, were synthesized by hydrolysis of the condensation products from the appropriate benzyl bromide and ethyl acetamidomalonate and were compared with the corresponding 3-halotyrosines as growth inhibitors of Escherichia coli 9723, Streptococcus faecalis 8043 and Lactobacillus plantarum 8014. In contrast to the 2- and 3-fluorotyrosines which were equally effective as growth inhibitors, the 2-chloro- and 2-bromotyrosines were much more effective than the 3-chloro- and 3-bromotyrosines in inhibiting the growth of the three microorganisms. For each of the assay organisms, the growth inhibitions of all three 2-halotyrosines were reversed competitively in varying degrees by tyrosine.

In vitro antimicrobial activity of some cyclic hydroxamic acids and related lactams.

Abstract: Against Enterobacter aerogenes 13048, Serratia marcescens 13880, Klebsiella pneumoniae 10031, Pseudomonas aeruginosa 10145, Escherichia coli 9723, Lactobacillus casei 7469, Lactobacillus plantarum 8014, Leuconostoc dextranicum 8086, and Streptococcus faecalis 8043, the mean minimal inhibitory concentrations of three cyclic hydroxamic acids, 3-amino-3,4-dihydro-1-hydroxycarbostyril, the 6-chloro analog, and the 7-chloro analog, were 0.6, 0.6, and 0.2 micrograms/ml, and those of the corresponding lactams, 3-amino-3,4-dihydrocarbostyril, the 6-chloro analog, and the 7-chloro analog, were 60, 60, and 6 micrograms/ml, respectively. Under the same assay conditions the mean minimal inhibitory concentrations of chloramphenicol and kanamycin were both 2 micrograms/ml. In addition, the cyclic hydroxamic acids but not the lactams inhibited the growth of Candida albicans at minimal inhibitory concentrations ranging from 20 to 200 micrograms/ml, at pH 7, as compared with that of amphotericin B, at 2 micrograms/ml.

Synthesis and microbiological activities of some monohalogenated analogs of tyrosine

Abstract: 2-Chlorotyrosine and 2-bromotyrosine, as well as the previously reported 2-fluorotyrosine, were synthesized by hydrolysis of the condensation products from the appropriate benzyl bromide and ethyl acetamidomalonate and were compared with the corresponding 3-halotyrosines as growth inhibitors of Escherichia coli 9723, Streptococcus faecalis 8043 and Lactobacillus plantarum 8014. In contrast to the 2- and 3-fluorotyrosines which were equally effective as growth inhibitors, the 2-chloro- and 2-bromotyrosines were much more effective than the 3-chloro- and 3-bromotyrosines in inhibiting the growth of the three microorganisms. For each of the assay organisms, the growth inhibitions of all three 2-halotyrosines were reversed competitively in varying degrees by tyrosine.

Synthesis and antibacterial activities of some chloro analogs of 3-amino-3,4-dihydro-1-hydroxycarbostyril

Abstract: The effects of a chloro substituent upon the microbiological activities of 3-amino-3,4-dihydro-1-hydroxycarbostyril were determined. The 5-, 6-, and 7-chloro analogs were synthesized by reductive cyclizations of the appropriately chloro-substituted o-nitrophenylalanines, while the 8-chloro analog was obtained from the N-trifluoroacetyl-3-chloro-2-nitrophenylalanine ethyl ester. All of these compounds were observed to inhibit the growth of Escherichia coli 9723, Leuconostoc dextranicum 8086, and Lactobacillus plantarum 8014. The relative inhibitory activities of the chloro analogs were 7-Cl greater than 6-Cl greater than 8-Cl greater than 5-Cl in E. coli and 7-Cl greater than 6-Cl greater than 8-Cl = 5-Cl in L. dextranicum and L. plantarum. In each of the three microorganisms, the 7-Cl analog was a more effective growth inhibitor than the parent unsubstituted compound. The growth inhibitory activities of this class of compounds were demonstrated to be much more effective than those of the four corresponding lactams, the 5-, 6-, 7-, and 8-chloro analogs of 3-amino-3,4-dihydrocarbostyril.

Fluorinated amino acids: compatibility with native protein structures and effects on protein–protein interactions

Abstract: Fluorinated analogues of the canonical α-L-amino acids have gained widespread attention as building blocks that may endow peptides and proteins with advantageous biophysical, chemical and biological properties. This critical review covers the literature dealing with investigations of peptides and proteins containing fluorinated analogues of the canonical amino acids published over the course of the past decade including the late nineties. It focuses on side-chain fluorinated amino acids, the carbon backbone of which is identical to their natural analogues. Each class of amino acids—aliphatic, aromatic, charged and polar as well as proline—is presented in a separate section. General effects of fluorine on essential properties such as hydrophobicity, acidity/basicity and conformation of the specific side chains and the impact of these altered properties on stability, folding kinetics and activity of peptides and proteins are discussed (245 references).

Eosinophils generate brominating oxidants in allergen-induced asthma

Abstract: Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific “molecular fingerprint” for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.

3-Bromotyrosine and 3,5-dibromotyrosine are major products of protein oxidation by eosinophil peroxidase: potential markers for eosinophil-dependent tissue injury in vivo.

Abstract: Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps ...

Ligand-Enabled β-C–H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary

Abstract: Pd-catalyzed β-C–H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C–H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct β-C–H activation, albeit this system was not compatible with carboxylic acids containing α-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of β-arylation of carboxylic acid derivatives, especially α-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.

Degradation Studies on Benzoxazinoids. Soil Degradation Dynamics of 2,4-Dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and Its Degradation Products, Phytotoxic Allelochemicals from Gramineae

Abstract: Benzoxazinoids have been described as important allelochemicals from Gramineae as well as Acanthaceae, Rannunculaceae, and Scrophulariaceae plants. Several bioactivities have been described and evaluated for these compounds, including fungistatic, antifeedant, and phytotoxic. In ongoing studies about allelochemicals as natural herbicide models, the description of soil dynamics in phytotoxic agents has high importance, because the possible biotransformations developed by soil microorganisms could yield compounds with modified biological properties, affecting the overall allelopathic capability of the producer plant in a direct manner. Thus, a complete degradation study has been carried out for 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and 6-methoxybenzoxazolin-2(3H)-one (MBOA) in two soils cultivated with Triticum aestivum L. varieties (cv. Astron and cv. Ritmo). The main purpose was to identify degradation products and to elucidate biotransformation dynamics. Results show DIMBOA to degrade rapidly, yielding MBOA in both studied soils at different doses (t(1/2) = 31 +/- 1 h, n = 12) and reaching high conversions (80 +/- 4 h, n = 42). MBOA, an intermediate in the degradation pathway from DIMBOA to 2-amino-7-methoxy-3H-phenoxazin-3-one (AMPO), was more resistant toward biodegradation (t(1/2) = 5 +/- 1 days, n = 6). MBOA showed maximum conversions at a dose of 250 mg/kg of soil (36 +/- 3 days, n = 6). Soil belonging to T. aestivum cv. Ritmo crops showed higher degradation capacity than cv. Astron soil. AMPO was the final degradation product observed for DIMBOA in the soils and experimental conditions selected. Consequences for activity and stability of these compounds in relation to allelopathy are discussed.