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Articles 1 - 24 of 24
Full-Text Articles in Life Sciences
In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D.
In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D.
Chemistry: Faculty Publications and Other Works
The landscape of viral strains and lineages of SARS-CoV-2 keeps changing and is currently dominated by Delta and Omicron variants. Members of the latest Omicron variants, including BA.1, are showing a high level of immune evasion, and Omicron has become a prominent variant circulating globally. In our search for versatile medicinal chemistry scaffolds, we prepared a library of substituted α-aminocyclobutanones from an α-aminocyclobutanone synthon (11). We performed an in silico screen of this actual chemical library as well as other virtual 2-aminocyclobutanone analogs against seven SARS-CoV-2 nonstructural proteins to identify potential drug leads against SARS-CoV-2, and more broadly against coronavirus …
Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah
Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah
Chemistry: Faculty Publications and Other Works
Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …
Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah
Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah
Chemistry: Faculty Publications and Other Works
SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …
Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li
Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li
Chemistry: Faculty Publications and Other Works
Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r …
A Review Of The Preclinical And Clinical Efficacy Of Remdesivir, Hydroxychloroquine, And Lopinavir-Ritonavir Treatments Against Covid-19, Dawid Maciorowski, Samir Z. El Idrissi, Yash Gupta, Brian J. Medernach, Michael B. Burns, Daniel P. Becker Ph.D., Ravi Durvasula, Prakasha Kempaiah
A Review Of The Preclinical And Clinical Efficacy Of Remdesivir, Hydroxychloroquine, And Lopinavir-Ritonavir Treatments Against Covid-19, Dawid Maciorowski, Samir Z. El Idrissi, Yash Gupta, Brian J. Medernach, Michael B. Burns, Daniel P. Becker Ph.D., Ravi Durvasula, Prakasha Kempaiah
Chemistry: Faculty Publications and Other Works
In December of 2019, an outbreak of a novel coronavirus flared in Wuhan, the capital city of the Hubei Province, China. The pathogen has been identified as a novel enveloped RNA beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus SARS-CoV-2 is associated with a disease characterized by severe atypical pneumonia known as coronavirus 2019 (COVID-19). Typical symptoms of this disease include cough, fever, malaise, shortness of breath, gastrointestinal symptoms, anosmia, and, in severe cases, pneumonia.1 The high-risk group of COVID-19 patients includes people over the age of 60 years as well as people with existing cardiovascular …
Indoline‐6‐Sulfonamide Inhibitors Of The Bacterial Enzyme Dape, Cory T. Reidl, Tahirah K. Heath, Iman Darwish, Rachel M. Torrez, Maxwell Moore, Elliot Gild, Boguslaw P. Nocek, Anna Starus, Richard C. Holz, Daniel P. Becker Ph.D.
Indoline‐6‐Sulfonamide Inhibitors Of The Bacterial Enzyme Dape, Cory T. Reidl, Tahirah K. Heath, Iman Darwish, Rachel M. Torrez, Maxwell Moore, Elliot Gild, Boguslaw P. Nocek, Anna Starus, Richard C. Holz, Daniel P. Becker Ph.D.
Chemistry: Faculty Publications and Other Works
Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).
Synthesis Of A Protected 2-Aminocyclobutanone As A Modular Transition State Synthon For Medicinal Chemistry, Thahani S. Habeeb Mohammad, Cory T. Reidl, Matthias Zeller, Daniel P. Becker Ph.D.
Synthesis Of A Protected 2-Aminocyclobutanone As A Modular Transition State Synthon For Medicinal Chemistry, Thahani S. Habeeb Mohammad, Cory T. Reidl, Matthias Zeller, Daniel P. Becker Ph.D.
Chemistry: Faculty Publications and Other Works
The hydrochloride salt of ɑ-aminocyclobutanone protected as its dimethyl acetal 2,2-dimethoxycyclobutan-1-aminium chloride (3) has been prepared as a modular synthon for convenient access to cyclobutanone-containing lead inhibitors of hydrolase enzymes including serine proteases and metalloproteases. Protected ɑ-aminocyclobutanone 3 was converted to representative amide and sulfonamide-functionalized 2-aminocyclobutanone derivatives. Reaction of the amino acetal 3 with phenyl isothiocyanate afforded the bicyclic urea 1-hydroxyl-2,4-diazabicyclo[3.2.0]heptane-3-thione (9) as confirmed by a single crystal X-ray structure.
Laser Surface Cleaning As A Novel Approach For Genesis Solar Wind Collectors, Martina Schmeling, I. V. Veryovkin, C. E. Tripa
Laser Surface Cleaning As A Novel Approach For Genesis Solar Wind Collectors, Martina Schmeling, I. V. Veryovkin, C. E. Tripa
Chemistry: Faculty Publications and Other Works
A new surface cleaning method utilizing lasers has been evaluated for its suitability to Genesis solar wind collectors
Total Reflection X-Ray Fluorescence, Martina Schmeling
Total Reflection X-Ray Fluorescence, Martina Schmeling
Chemistry: Faculty Publications and Other Works
Total reflection X-ray fluorescence (TXRF) spectrometry is a non-destructive and surface sensitive multi-element analytical method based on energy dispersive X-ray fluorescence spectrometry with detection limits in the lower picogram range. It utilizes the total reflection of the primary X-ray beam at or below the critical angle of incidence. At this angle, the fluorescence intensity is substantially enhanced for samples present as small granular residue or as thin homogenous layer deposited at the surface of a thick substrate. Generally, two types of application exist: micro- and trace-analysis as well as surface and thin-layer analysis. For micro- and traceanalysis, a small amount …
A Gcn5-Related N-Acetyltransferase (Gnat) Capable Of Acetylating Polymyxin B And Colistin Antibiotics In Vitro, Mateusz P. Czub, Brian Zhang, M. Paul Chiarelli, Karolina A. Majorek, Layton Joe, Pryemyslaw J. Prebski, Alina Revilla, Weiming Wu, Daniel P. Becker, Wladek Minor, Misty L. Kuhn
A Gcn5-Related N-Acetyltransferase (Gnat) Capable Of Acetylating Polymyxin B And Colistin Antibiotics In Vitro, Mateusz P. Czub, Brian Zhang, M. Paul Chiarelli, Karolina A. Majorek, Layton Joe, Pryemyslaw J. Prebski, Alina Revilla, Weiming Wu, Daniel P. Becker, Wladek Minor, Misty L. Kuhn
Chemistry: Faculty Publications and Other Works
Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an …
Resurrecting The Regulatory Properties Of The Ostreococcus Tauri Adp-Glucose Pyrophosphorylase Large Subunit, Carlos M. Figueroa, Misty L. Kuhn, Benjamin L. Hill, Alberto A. Iglesias, Miguel A. Ballicora
Resurrecting The Regulatory Properties Of The Ostreococcus Tauri Adp-Glucose Pyrophosphorylase Large Subunit, Carlos M. Figueroa, Misty L. Kuhn, Benjamin L. Hill, Alberto A. Iglesias, Miguel A. Ballicora
Chemistry: Faculty Publications and Other Works
ADP-glucose pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step for the synthesis of glycogen in cyanobacteria and starch in green algae and plants. The enzyme from cyanobacteria is homotetrameric (α4), while that from green algae and plants is heterotetrameric (α2β2). These ADP-Glc PPases are allosterically regulated by 3-phosphoglycerate (3PGA, activator) and inorganic orthophosphate (Pi, inhibitor). Previous studies on the cyanobacterial and plant enzymes showed that 3PGA binds to two highly conserved Lys residues located in the C-terminal domain. We observed that both Lys residues are present in the small (α) subunit of the Ostreococcus tauri enzyme; however, one of these …
Starch Synthesis In Ostreococcus Tauri: The Starch-Binding Domains Of Starch Synthase Iii-B Are Essential For Catalytic Activity, Julieta Barchiesi, Maria Belen Velazquez, Nicolas Palopoli, Alberto A. Iglesias, Diego F. Gomez-Casati, Miguel A. Ballicora, Maria Victoria Busi
Starch Synthesis In Ostreococcus Tauri: The Starch-Binding Domains Of Starch Synthase Iii-B Are Essential For Catalytic Activity, Julieta Barchiesi, Maria Belen Velazquez, Nicolas Palopoli, Alberto A. Iglesias, Diego F. Gomez-Casati, Miguel A. Ballicora, Maria Victoria Busi
Chemistry: Faculty Publications and Other Works
Starch is the major energy storage carbohydrate in photosynthetic eukaryotes. Several enzymes are involved in building highly organized semi-crystalline starch granules, including starch-synthase III (SSIII), which is widely conserved in photosynthetic organisms. This enzyme catalyzes the extension of the α-1,4 glucan chain and plays a regulatory role in the synthesis of starch. Interestingly, unlike most plants, the unicellular green alga Ostreococcus tauri has three SSIII isoforms. In the present study, we describe the structure and function of OsttaSSIII-B, which has a similar modular organization to SSIII in higher plants, comprising three putative starch-binding domains (SBDs) at the N-terminal region and …
On The Roles Of Wheat Endosperm Adp-Glucose Pyrophosphorylase Subunits, Danisa M. L. Ferrero, Matias D. Asencion Diez, Misty L. Kuhn, Christine A. Falaschetti, Claudia V. Piattoni, Alberto A. Iglesias, Miguel A. Ballicora
On The Roles Of Wheat Endosperm Adp-Glucose Pyrophosphorylase Subunits, Danisa M. L. Ferrero, Matias D. Asencion Diez, Misty L. Kuhn, Christine A. Falaschetti, Claudia V. Piattoni, Alberto A. Iglesias, Miguel A. Ballicora
Chemistry: Faculty Publications and Other Works
The ADP-glucose pyrophosphorylase from wheat endosperm controls starch synthesis in seeds and has unique regulatory properties compared to others from this family. It comprises two types of subunits, but despite its importance little is known about their roles. Here, we synthesized de novo the wheat endosperm ADP-glucose pyrophosphorylase small (S) and large (L) subunit genes, heterologously expressed them in Escherichia coli, and kinetically characterized the recombinant proteins. To understand their distinct roles, we co-expressed them with well characterized subunits from the potato tuber enzyme to obtain hybrids with one S subunit from one source and an L subunit from …
Folding Of Gα Subunits: Implications For Disease States, Matthew Najor, Brian D. Leverson, Jesse L. Goossens, Saad Kothawala, Kenneth W. Olsen, Duarte Mota De Freitas
Folding Of Gα Subunits: Implications For Disease States, Matthew Najor, Brian D. Leverson, Jesse L. Goossens, Saad Kothawala, Kenneth W. Olsen, Duarte Mota De Freitas
Chemistry: Faculty Publications and Other Works
G-proteins play a central role in signal transduction by fluctuating between “on” and “off” phases that are determined by a conformational change. cAMP is a secondary messenger whose formation is inhibited or stimulated by activated Giα1 or Gsα subunit. We used tryptophan fluorescence, UV/vis spectrophotometry, and circular dichroism to probe distinct structural features within active and inactive conformations from wild-type and tryptophan mutants of Giα1 and Gsα. For all proteins studied, we found that the active conformations were more stable than the inactive conformations, and upon refolding from higher temperatures, activated wild-type subunits recovered significantly more native structure. We also …
A Series Of 4- And 5-Coordinate Ni(Ii) Complexes: Synthesis, Characterization, Spectroscopic, And Dft Studies, Jack Ghannam, Talal Al Assil, Trey C. Pankratz, Richard L. Lord, Matthias Zeller, Wei-Tsung Lee
A Series Of 4- And 5-Coordinate Ni(Ii) Complexes: Synthesis, Characterization, Spectroscopic, And Dft Studies, Jack Ghannam, Talal Al Assil, Trey C. Pankratz, Richard L. Lord, Matthias Zeller, Wei-Tsung Lee
Chemistry: Faculty Publications and Other Works
A series of four- and five-coordinate Ni(II) complexes CztBu(PyriPr)2NiX (1–3 and 1·THF–3·THF), where X = Cl, Br, and I, were synthesized and fully characterized by NMR and UV–vis spectroscopy, X-ray crystallography, cyclic voltammetry, and density functional theory calculations. The solid-state structures of 1–3 reveal rare examples of seesaw Ni(II) complexes. In solution, 1–3 bind reversibly to a THF molecule to form five-coordinate adducts. The electronic transitions in the visible region (630–680 nm), attributed to LMCT bands, for 1 → 3 exhibit a …
Practical Spectrophotometric Assay For The Dape-Encoded N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase, A Potential Antibiotic Target, Tahira K. Heath, Marlon R. Lutz Jr., Cory T. Reidl, Estefany R. Guzman, Claire A. Herbert, Boguslaw P. Nocek, Richard C. Hotz, Kenneth W. Olsen, Miguel A. Ballicora, Daniel P. Becker
Practical Spectrophotometric Assay For The Dape-Encoded N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase, A Potential Antibiotic Target, Tahira K. Heath, Marlon R. Lutz Jr., Cory T. Reidl, Estefany R. Guzman, Claire A. Herbert, Boguslaw P. Nocek, Richard C. Hotz, Kenneth W. Olsen, Miguel A. Ballicora, Daniel P. Becker
Chemistry: Faculty Publications and Other Works
A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6 …
Crystal Structure Of (2-{[(8-AminonaPhthalen-1-Yl)Imino]MethYl}-4,6-Di-Tert-ButylPhenolato-Κ3n,N′,O)BromidoNickel(Ii), Patrick O’Brien, Matthias Zeller, Wei-Tsung Less
Crystal Structure Of (2-{[(8-AminonaPhthalen-1-Yl)Imino]MethYl}-4,6-Di-Tert-ButylPhenolato-Κ3n,N′,O)BromidoNickel(Ii), Patrick O’Brien, Matthias Zeller, Wei-Tsung Less
Chemistry: Faculty Publications and Other Works
The title compound, [NiBr(C25H29N2O)], contains an NiII atom with a slightly distorted square-planar coordination environment defined by one O and two N atoms from the 2-{[(8-aminonaphthalen-1-yl)imino]methyl}-4,6-di-tert-butylphenolate ligand and a bromide anion. The Ni—O and Ni—N bond lengths are slightly longer than those observed in the phenyl backbone counterpart, which can be attributed to the larger steric hindrance of the naphthyl group in the structure of the title compound. The molecule as a whole is substantially distorted, with both the planar naphthalene-1,8-diamine and imino–methyl– phenolate substitutents rotated against the NiN2OBr plane by 38.92 (7) and 37.22 (8), respectively, giving the molecule …
Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz
Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz
Chemistry: Faculty Publications and Other Works
The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to …
Generating Enzyme And Radical‐Mediated Bisubstrates As Tools For Investigating Gcn5‐Related N‐Acetyltransferases, Cory T. Reidl, Karolina A. Majorek, Joseph Dang, David Tran, Kristen Jew, Melissa Law, Yasmine Payne, Wladek Minor, Daniel P. Becker, Misty L. Kuhn
Generating Enzyme And Radical‐Mediated Bisubstrates As Tools For Investigating Gcn5‐Related N‐Acetyltransferases, Cory T. Reidl, Karolina A. Majorek, Joseph Dang, David Tran, Kristen Jew, Melissa Law, Yasmine Payne, Wladek Minor, Daniel P. Becker, Misty L. Kuhn
Chemistry: Faculty Publications and Other Works
Gcn5‐related N‐acetyltransferases (GNATs) are found in all kingdoms of life and catalyze important acyl transfer reactions in diverse cellular processes. While many 3D structures of GNATs have been determined, most do not contain acceptor substrates in their active sites. To expand upon existing crystallographic strategies for improving acceptor‐bound GNAT structures, we synthesized peptide substrate analogs and reacted them with CoA in PA4794 protein crystals. We found two separate mechanisms for bisubstrate formation: (a) a novel X‐ray induced radical‐mediated alkylation of CoA with an alkene peptide and (b) direct alkylation of CoA with a halogenated peptide. Our approach is widely …
Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu
Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu
Chemistry: Faculty Publications and Other Works
The Bacillus subtilis protein regulator of the gabTD operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5′-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the “active site” in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands. A reactive GABA analog, ( …
An Analytical Method For Detecting Toxic Metal Cations Using Cyclotriveratrylene Derivative Capped Gold Nanoparticles, Zachary R. Osner, Richard C. Holz, Daniel P. Becker Ph.D.
An Analytical Method For Detecting Toxic Metal Cations Using Cyclotriveratrylene Derivative Capped Gold Nanoparticles, Zachary R. Osner, Richard C. Holz, Daniel P. Becker Ph.D.
Chemistry: Faculty Publications and Other Works
Cyclotriveratrylene-oxime (CTV-oxime) derivatives that terminate with a dithiolate linker were synthesized enabling the supramolecular scaffold to adhere to gold nanoparticles (AuNPs) with the bowl-shaped cavity of the CTV scaffold exposed for utilization in host–guest chemistry. Exposure of these CTV functionalized AuNPs to varying concentrations of di- and trivalent metal cations resulted in the formation of large CTV-AuNP polymeric clusters and an accompanying a shift in the plasmon resonance. These interactions between the CTV-AuNPs and the metal cations in solution provides proof-of-concept that supramolecular functionalized AuNPs can be used as a simple and straightforward, on-site detection system for toxic metal cations …
Metal-Free Tandem Beckmann–Electrophilic Aromatic Substitution Cascade Affording Diaryl Imines, Ketones, Amines, And Quinazolines, Samuel Sarsah, Marlon R. Lutz Jr., Kailyn Chichi Bobb, Daniel Becker
Metal-Free Tandem Beckmann–Electrophilic Aromatic Substitution Cascade Affording Diaryl Imines, Ketones, Amines, And Quinazolines, Samuel Sarsah, Marlon R. Lutz Jr., Kailyn Chichi Bobb, Daniel Becker
Chemistry: Faculty Publications and Other Works
A cascade reaction sequence involving a Beckmann rearrangement on benzophenone oxime followed by an electrophilic aromatic substitution (EAS) on the intermediate nitrilium ion affords N-phenyl diaryl imines that may then be hydrolyzed to ketones, or reduced to the corresponding amines. Reaction with benzonitrile afforded 2,4-diphenylquinazoline through a Beckmann–Ritter–EAS cascade.
Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta M. Gillner, Daniel P. Becker Ph.D., Richard C. Holz
Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta M. Gillner, Daniel P. Becker Ph.D., Richard C. Holz
Chemistry: Faculty Publications and Other Works
In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.
A Proposal For United States/Polish Collaboration On Energy And The Environment, Carole B. Szpunar
A Proposal For United States/Polish Collaboration On Energy And The Environment, Carole B. Szpunar
Chemistry: Faculty Publications and Other Works
Argonne National Laboratory, a U.S. Department of Energy facility that is operated by the University of Chicago and located southwest of Chicago, Illinois, has proposed a collaborative effort by the United States and Poland to conduct applied research on energy and environmental topics of common interest. Through this collaboration, evaluative studies on energy and environmental assessment issues could be developed and implemented by Argonne and one or more sister institutions in Poland, which could lead to active research, development, and demonstration joint activities. The objective of this initiative is to produce strategies and options for review by Poland's decision makers …