Douglas W. Winters

Bio: Douglas W. Winters is an academic researcher. The author has contributed to research in topics: Benzyl bromide & Lactobacillus plantarum. The author has an hindex of 1, co-authored 2 publications receiving 17 citations.

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 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.

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 ...

Characterization of pu-erh tea using chemical and metabolic profiling approaches.

Abstract: In this study, the chemical constituents of pu-erh tea, black tea, and green tea, as well as those of pu-erh tea products of different ages, were analyzed and compared using a chemical profiling approach. Differences in tea processing resulted in differences in the chemical constituents and the color of tea infusions. Human biological responses to pu-erh tea ingestion were also studied by using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with multivariate statistical techniques. Metabolic alterations during and after pu-erh tea ingestion were characterized by increased urinary excretion of 5-hydroxytryptophan, inositol, and 4-methoxyphenylacetic acid, along with reduced excretion of 3-chlorotyrosine and creatinine. This study highlights the potential for metabonomic technology to assess nutritional interventions and is an important step toward a full understanding of pu-erh tea and its influence on human metabolism.