A5070671745- Microbial Natural Products and Biosynthesis
- Synthetic Organic Chemistry Methods
- Organometallic Complex Synthesis and Catalysis
- Bacterial Genetics and Biotechnology
- Drug Solubulity and Delivery Systems
- Cyclopropane Reaction Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- DNA Repair Mechanisms
- Inorganic and Organometallic Chemistry
- Chemical synthesis and alkaloids
- Computational Drug Discovery Methods
- Protein purification and stability
- Traditional and Medicinal Uses of Annonaceae
- Carbon dioxide utilization in catalysis
- Carbohydrate Chemistry and Synthesis
- Genomics and Phylogenetic Studies
- Polyamine Metabolism and Applications
- Inorganic Chemistry and Materials
- PI3K/AKT/mTOR signaling in cancer
- Gene expression and cancer classification
- Quinazolinone synthesis and applications
- RNA and protein synthesis mechanisms
- Synthesis and characterization of novel inorganic/organometallic compounds
- Hydrogels: synthesis, properties, applications
- Sphingolipid Metabolism and Signaling
Winthrop University
2021
Harvard University
2015-2020
Vertex Pharmaceuticals (United States)
2019
Queen's University Belfast
2012-2016
University of Notre Dame
2012-2015
Notre Dame of Dadiangas University
2015
Reproductive Science Center
2012
National Institute of Environmental Health Sciences
2012
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2012
National Institutes of Health
2012
Certain Escherichia coli strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated colorectal cancer pathogenesis. However, colibactin's chemical structure and molecular mechanism underlying its genotoxic effects have remained unknown for more than decade. Here we combine an untargeted DNA adductomics approach with synthesis to identify characterize covalent modification from cell lines treated colibactin-producing E. Our data establish that colibactin...
Certain commensal and pathogenic bacteria produce colibactin, a small-molecule genotoxin that causes interstrand cross-links in host cell DNA. Although colibactin alkylates DNA, the molecular basis for cross-link formation is unclear. Here, we report biosynthetic enzyme ClbL an amide bond-forming links aminoketone β-keto thioester substrates vitro vivo. The substrate specificity of strongly supports role this terminating NRPS-PKS assembly line incorporating two electrophilic cyclopropane...
Colibactin is a structurally uncharacterized, genotoxic natural product produced by commensal and pathogenic strains of E. coli that harbor the pks island. A new metabolite has been isolated from pks+ mutant missing an essential biosynthetic enzyme. The unusual azaspiro[2.4] bicyclic ring system this molecule provides insights into colibactin biosynthesis suggests mechanism through which other pks-derived metabolites may exert genotoxicity.
Colibactin is a human gut bacterial genotoxin of unknown structure that has been linked to colon cancer. The biosynthesis this elusive metabolite directed by the pks gene cluster, which encodes hybrid nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line hypothesized use unusual polyketide building block aminomalonate. This biosynthetic pathway thought initially produce an inactive intermediate (precolibactin) processed active toxin. Here, we report first in vitro...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe quantitative analysis of ligand effects (QALE). The aryl effectMatthew R. Wilson, David C. Woska, Alfred Prock, and Warren P. GieringCite this: Organometallics 1993, 12, 5, 1742–1752Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 1993https://pubs.acs.org/doi/10.1021/om00029a035https://doi.org/10.1021/om00029a035research-articleACS PublicationsRequest reuse permissionsArticle...
Through the quantitative analysis of ligand effects (QALE), we have probed π associated with Rh−P bond lengths, νCO, and −ΔHrx for Rh(CO)(Cl)(PX3)2 νCO Rh(acac)(CO)(PZ3). It was found that are complex depend strongly on nature ancillary or other participatory groups. The results QALE point out importance synergistic interactions between PZ3 ligands in accord theoretical computations. Literature data Rh(CO)(Cl)(PZ3)2 been supplemented new values ΔHrx PMe3 (−75.6 ± 0.3 kcal/mol), P(i-Pr)3...
Using the QALE model, we determined stereoelectronic parameters for following ligands: P(CF3)3 (χd = 33 ± 2, θ 137 13°, Ear 0, πp 11.1 0.6), P(CH2CH2C6F13)3 9 3, 2°, 2.5 0.4), P[p-(F13C6)C6H4]3 23 1, 145°, 2.7, 0), and P(C6F5)3 34 191 4.3 0.5, 0). In addition, evaluated P[Pyr-3,4-(CO2Et)2]3 (Pyr pyrrolyl; χd 43 3.3, 2 1). Revised PF3 are also presented: 110 24°, 13.2 0.5. The absence of an indicated error means that these values were assigned initially to particular in analyses or...
In this paper we show how graphical analysis of ligand effect data for families ligands should be combined with regression in order to gain a more self-consistent interpretation results. If steric threshold shows up the trialkyl (AR3), then must full set data. Similarly, dependence isosteric A(p-XC6H4)3 have same on electronic parameter χ that find Finally, both AR3 and vividly whether effects and/or aryl belong analysis. Thus, results any acceptable, they consistent
The kinamycin family of aromatic polyketide natural products contains an atypical angucycline ring system substituted with a diazo group. enzymatic chemistry involved in constructing both these structural features has been largely unexplored. Here we report the vivo and vitro production seongomycin, shunt product from this pathway, stealthin C, proposed biosynthetic precursor to kinamycins. We show that single enzyme, flavin-dependent monooxygenase AlpJ, can generate metabolites...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReinvestigation of the oxidative addition methyl iodide, hydrogen, and oxygen to Ir(CO)(Cl)L2. Quantitative analysis ligand effects (QALE)Matthew R. Wilson, Hongye Liu, Alfred Prock, Warren P. GieringCite this: Organometallics 1993, 12, 6, 2044–2050Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June...
Comparison of pairs physiochemical properties phosphines and their complexes demonstrates that, in general, at least four independent stereoelectronic parameters are general required to describe the variations these properties. Consequently, any two-parameter model such as Drago's E/C will have limited use correlation analyses involving phosphines. The QALE analysis EB CB shows that linear combinations χ θ, with a small contribution from Ear. Thus, successful application be restricted...
The solution conformation behavior of the macrolide core microtubule-stabilizing agents (−)-zampanolide and (−)-dactylolide has been determined through a combination high-field NMR experiments computational modeling. Taken together, results demonstrate that in both molecules exist as mixture three interconverting conformational families, one which bears strong resemblance to zampanolide's tubulin-bound conformation.
This research examined the application of hot melt extrusion (HME) in preparation matrix formulations containing hydroxypropyl cellulose (HPC) as a base polymer combination with methyl (MC) and methylcellulose (HPMC).The limit to which could control drug release under varying paddle speeds, high alcohol environments low loads was investigated on Caleva 10 ST dissolution tester. Rheological studies plate imaging highlighted impact thermoresponsive polymers release. The rate percentage were...
Progress toward the synthesis of microtubule-stabilizing agent, (-)-zampanolide, is reported. Construction 2,6-cis-tetrahydropyran ring was accomplished utilizing ether transfer methodology in conjunction with an intramolecular radical cyclization reaction. Efficient installation C16-C20 side chain relied on a one-pot cross-metathesis/olefination sequence, Sharpless epoxidation, and selective reduction vinyl epoxide.
The gut bacterial genotoxin colibactin is linked to the development of colorectal cancer. In final stages colibactin's biosynthesis, an inactive precursor (precolibactin) undergoes proteolytic cleavage by ClbP, unusual inner-membrane-bound periplasmic peptidase, generate active genotoxin. This enzyme presents opportunity monitor and modulate but its form has not been studied in vitro limited tools exist measure activity. Here, we describe biochemical characterization catalytically active,...
Abstract Gespannte Moleküle sind von außerordentlichem Interesse in der Chemie, und ihre hochenergetischen Bindungen dienen als “Treibstoff” für komplexe Synthesen. Entwicklungen auf diesem Gebiet führten jüngster Zeit zur vermehrten Nutzung gespannter Alkene Intermediate Naturstoffsynthese. Dieser Kurzaufsatz präsentiert diese neuen Fortschritte zusammen mit im Hinblick das Verständnis einzigartigen Reaktivität Alkene.
Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding the conformational preferences macrolide core in both natural products, we hypothesized that analogues lacking C17-methyl group would maintain necessary conformation for bioactivity while reducing number synthetic manipulations their synthesis. Analogues 3, 4 5 were prepared via total synthesis, determined through computational...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies of the oxidatively promoted carbonylation .eta.-Cp(CO)(L)FeMe in methylene chloride. Applications quantitative analysis ligand effectsAlfred Prock, Warren P. Giering, Jack E. Greene, Randy Meirowitz, Steven L. Hoffman, David C. Woska, Matthew Wilson, Richard Chang, Jianxiang Chen, and Cite this: Organometallics 1991, 10, 3479–3485Publication Date (Print):October 1, 1991Publication History Published online1 May 2002Published inissue 1...