Research & Discoveries

Chem & Biochem Collab: How a tiny enzyme helps build a big brain

Many enzymes use radical chemistry to build essential molecules, but radicals are highly reactive and can easily cause damage if not tightly controlled. The study by the labs of Profs. Ken Yokoyama, Pei Zhou, and Weitao Yang of the Chemistry Department reveals how a radical-generating enzyme, MoaA, from the radical S-adenosyl-L-methionine (SAM) superfamily, senses when its correct substrate is bound and safely triggers the radical reaction. Using a combination of nuclear magnetic resonance (NMR) and electron… read more about Chem & Biochem Collab: How a tiny enzyme helps build a big brain »

Changing Drug Manufacturing One Enzyme at a Time

Professor Kenichi Yokoyama and team have showed that a newly discovered enzyme is sufficient to make azetidine, an organic compound and a building block of a wide range of therapeutics, including antibiotics, antiviral drugs, and cancer treatments.    Rather than relying on harsh solvents and toxic chemicals, the team discovered enzymes, PolF and PolE, that produce azetidine from an inexpensive precursor compound in water.   “The two enzymes that we discovered are functionally and structurally… read more about Changing Drug Manufacturing One Enzyme at a Time »

Understanding the Reaction Energetics of Oxygen-evolving Electrocatalysts

Electrocatalysts can produce valuable chemicals with electricity, but current electrocatalysts suffer from slow reaction kinetics. The chemical composition of electrocatalysts is known  to have a big impact on catalyst activity, but exactly why certain compositions lead to a better catalyst is not known. In this work, the Moreno-Hernandez laboratory developed electrochemical methods to determine thermodynamic and kinetic information about reaction intermediates involved in electrocatalysis. These methods were applied… read more about Understanding the Reaction Energetics of Oxygen-evolving Electrocatalysts »

Yokoyama Lab Found the Novel Reactivity of an Fe-dependent Oxidase in Antifungal Biosynthesis

In a recently published study available in the Journal of the American Chemical Society, the Yokoyama lab characterized the mechanism of oxidative C-C bond cleavage reaction catalyzed by Fe and 2-oxoglutarate (2-OG)-dependent oxidase, PolD. This enzyme diverges the biosynthetic pathways between C6 and C7-sugar nucleoside antifungals, and therefore, its mechanistic and structural understanding is important for the future genome-mining discovery of novel antifungals. Most significantly, they found that the… read more about Yokoyama Lab Found the Novel Reactivity of an Fe-dependent Oxidase in Antifungal Biosynthesis »

New Catalytic Enantioselective Approach to 1,4-Diamines

The Malcolmson Lab has developed an enantio- and diastereoselective copper-catalyzed method for assembling chiral 1,4-diamines, nitrogen-containing molecules with broad applications in pharmaceuticals and ligand design for which there are few direct synthetic approaches. A research team led by former postdoc, Pengfei Zhou (now an assistant professor at Chongqing Medical University) and graduate student, Jiaqi Zhu, discovered the novel carbon–carbon bond-forming strategy that proceeds through reductive… read more about New Catalytic Enantioselective Approach to 1,4-Diamines »

Widenhoefer and Craig Labs Team Up to Make Advances in Further Understanding of Mechanically Coupled Ligand Effects in Catalysis

We love a collaboration!! The Widenhoefer and Craig Labs have teamed up to describe what they term multi-state mechanocatalysis (MMC), which they believe is the first demonstration that externally applied mechanical forces can be directed through a polymer network into single-site catalysts, using those forces to bias the outcome of a catalytic reaction. In a sense, MMC can be thought of as top-down atomic manipulation—pushing and pulling molecules into the optimal shape for a desired function (here, catalysis). The MMC is… read more about Widenhoefer and Craig Labs Team Up to Make Advances in Further Understanding of Mechanically Coupled Ligand Effects in Catalysis »

Franz Lab Targets Local Delivery (of active drugs, that is!)

Bacteria resistant to β-lactams, our largest class of antibiotics, pose a serious health threat. Our current catalog of antibiotics and their overuse has helped to select for bacteria possessing resistance enzymes, β-lactamases, capable of degrading all β-lactams antibiotics, greatly weakening our current arsenal and thwarting further antibiotic development efforts. Expression of these β-lactamases is typically a strength of resistant, pathogenic bacteria; the Franz lab designed a molecule to turn β-lactamase… read more about Franz Lab Targets Local Delivery (of active drugs, that is!) »

Hong Lab Opens New Avenues for Drug Discovery and Mechanistic Studies

Hyejin Lee and others in the Hong lab have successfully achieved an asymmetric total synthesis of 4,9,10-trihydroxyguaia-11(13)en-12,6-olide (1), a naturally occurring guaianolide with intriguing biological potential. This 20-step synthetic route has uncovered exciting new anticancer activity of the natural product against aggressive childhood tumors, opening new avenues for drug discovery and mechanistic studies. Learn more about their recent discoveries in an ACS Central Science article here.… read more about Hong Lab Opens New Avenues for Drug Discovery and Mechanistic Studies »

Moreno-Hernandez Lab Preserving Rare Elements Through Nanoscience

Noble metal oxides are materials that are incredibly rare on earth but also have incredible properties that make them useful for chemical transformations and renewable energy. In this work, the Moreno-Hernandez Lab discovered a way to grow these expensive materials on inexpensive supports that not only made better use of the material but also had synergistic effects that improved their properties. A key finding was that ruthenium oxide grown on titanium oxide, the same material that sunscreen is composed of, resulted in a… read more about Moreno-Hernandez Lab Preserving Rare Elements Through Nanoscience »

Promising Therapeutic Target for Pain Relief and Developing Non-addictive Pain Medications

Researchers in the Hong Lab, in collaboration with the Lee Lab (Department of Biochemistry) and the Ji Lab (Department of Anesthesiology), have recently published exciting new findings in Nature Communications on the development of a novel non-opioid pain medication. This research addresses the critical need for safer and more effective pain management strategies in the face of the ongoing opioid crisis. The team focused on the equilibrative nucleoside transporter subtype 1 (ENT1), a protein that regulates levels… read more about Promising Therapeutic Target for Pain Relief and Developing Non-addictive Pain Medications »

Revolutionizing the Treatment of Fungal Infections Through Modified Natural Products

Researchers in the Hong Lab, in collaboration with the Heitman Lab (Department of Molecular Genetics and Microbiology) and the Steinbach and Juvvadi Labs (University of Arkansas), have announced a significant advancement in the fight against fungal infections. They have developed a series of new antifungal drugs that show potent activity against harmful fungi while minimizing effects on the human immune system. Fungal infections pose a significant global health threat, but there are limited treatment options available.… read more about Revolutionizing the Treatment of Fungal Infections Through Modified Natural Products »

Combatting Drug-resistant Gram-negative Bacteria

The rise of multidrug-resistant Gram-negative bacteria is a serious threat to public health. To combat these dangerous pathogens, we urgently need new antibiotics that work differently than existing ones. One promising approach is to target lipid A biosynthesis, a critical process for maintaining the integrity of the bacterial cell wall and bacterial survival. Researchers in the Hong Lab, in collaboration with the Zhou (Department of Biochemistry) and Yang (Department of Chemistry) Labs, have developed promising… read more about Combatting Drug-resistant Gram-negative Bacteria »

Crystallization Fascination Leads to History Revisited

Professor Patrick Charbonneau has taken his knowledge of crystallization outside of the research lab and in to French-Canadian history. Charbonneau, an instructor of Chemistry 130L (The Chemistry and Physics of Cooking) has been using the example of fudge in his classes for several years to illustrate the polycrystalline structure of materials. It is when the time comes to find a source to explain the origin of the recipe that he runs into a problem: the available sources are "a bit of a mess," research hypotheses that are… read more about Crystallization Fascination Leads to History Revisited  »

Moreno-Hernandez Lab highlights the importance of understanding nanoscale dynamic restructuring

Hydrogen has the potential to be a great alternative to fossil fuels, specially “green hydrogen” which is produced by using electricity from renewable sources (e.g., wind, solar or hydroelectric) in devices called electrolyzers which split water into hydrogen and oxygen.Corrosion of catalysts inside electrolyzers is one of the main issues with the production of “green hydrogen” that prevents the adoption of electrolyzers at a global scale.The Moreno-Hernandez Laboratory focuses on understanding how the structure of these… read more about Moreno-Hernandez Lab highlights the importance of understanding nanoscale dynamic restructuring »

Ben Wiley Receives Clean Energy Research Innovation Award

Professor of Chemistry Ben Wiley was honored with the Cleantech Research Innovation Award at the Research Triangle Cleantech Cluster (RTCC)’s annual awards ceremony.The Cleantech Research Innovation Award recognizes an individual or team from industry or within an institution of higher education that is pursuing a research-based solution to a pressing cleantech challenge. Wiley’s work is focused on the reduction of industrial carbon emissions through the production of green hydrogen. Carbon emissions from the… read more about Ben Wiley Receives Clean Energy Research Innovation Award »

Becker Lab Expanding the Material Properties of 3D-printed Polyesters for Use in Drug Delivery Applications

The Becker Lab is expanding the material properties of 3D-printed poly (propylene fumarate-co-propylene succinate) copolyesters and their use in drug delivery applications. In their recent work, "Controlled Transdermal Delivery of Dexamethasone for Pain Management via Photochemically 3D-Printed Bioresorbable Microneedle Arrays", Becker lab members are fabricating poly(propylene fumarate-co-propylene succinate) oligomers into DXM-loaded, bioresorbable MAPs via continuous… read more about Becker Lab Expanding the Material Properties of 3D-printed Polyesters for Use in Drug Delivery Applications »

Warren Lab's Use of Pump-probe Microscopy for Art Restoration Featured in Laser Focus World

The Warren Lab's recent use of pump-probe microscopy for effective art restoration was featured in Laser Focus World. The lab built upon their mode-locked laser systems from the early 2000's, using pump-probe microscopy—a nonlinear optical imaging technique used to study chemical reactions. The lab uses ultrafast laser pulses of near-infrared (IR) light to allow for the identification of chemical compounds present in a paint pigment sample without invasive means. The team is now working… read more about Warren Lab's Use of Pump-probe Microscopy for Art Restoration Featured in Laser Focus World »

Malcolmson Lab Discovers Catalytic Z-Selective Ketone Aminoallylations to Prepare Vicinal Amino Tertiary Alcohols

The Malcolmson lab has discovered a reductive coupling of azatrienes and ketones for the Z-selective synthesis of allylic 1,2-amino tertiary alcohols. The strategy, developed by a team that was spearheaded by graduate student Jiaqi Zhu, provides an aminoallylation approach to this valuable pharmacophore that greatly expands upon the chemical space that is accessible for this moiety. The reaction is a rare example of a catalytic carbonyl allylation that forms a Z-alkene and two stereogenic centers and is… read more about Malcolmson Lab Discovers Catalytic Z-Selective Ketone Aminoallylations to Prepare Vicinal Amino Tertiary Alcohols »

Moreno-Hernandez Lab Finds the Importance of Nanoscale Heterogeneity

The Moreno-Hernandez Lab has their first Duke publication! In a recent JACS article, the Lab published findings that highlight the importance of nanoscale heterogeneity in determining macroscale properties such as electrocatalyst stability. Their efforts provide a characterization methodology that can be integrated into next-generation electrocatalyst discovery efforts. Check out their work, "Dissolution Heterogeneity Observed in Anisotropic Ruthenium Dioxide Nanocrystals via Liquid-… read more about Moreno-Hernandez Lab Finds the Importance of Nanoscale Heterogeneity »

Haas Lab Investigating Cu(I) binding to model peptides

The Haas Lab, with undergraduate researcher Abigail Strausbaugh Hjelmstad, facilitate a comparison of Cu(I) binding to six N-truncated amyloid beta (Aβ) model peptides and contribute to the understanding of the role of Aβ peptides as copper chelators in healthy and diseased brains in their recent publication, "Investigating Cu(I) binding to model peptides of N-terminal Aβ isoforms", available in the Journal of Inorganic Biochemistry. Learn more about their findings here! read more about Haas Lab Investigating Cu(I) binding to model peptides »

Therien Lab Realizes Low Band Gap One-dimensional Materials by Design

Metallic carbon nanotubes are one-dimensional tubular structures made up of hexagonally bonded sp2 carbon atoms. The Therien Lab has shown that by wrapping a metallic nanotube surface with rigid polymers, a semiconductor can be realized. This strategy contrasts with approaches that regulate electronic structural properties of bulk-phase materials which rely on altering the nature of covalent bonding. Reversible non-covalent polymer wrapping of metallic carbon nanotubes interconverts metallic and… read more about Therien Lab Realizes Low Band Gap One-dimensional Materials by Design »

Do the toxins of anionic nanoplastics have a possible role in Parkinson’s disease risk and progression?

Of the fastest growing neurological disorders in the world, Parkinson’s disease is pathologically defined by the accumulation of the protein α-synuclein in vulnerable neurons in the brain. Prolonged exposure to environmental challenges of largely unknown origins are suspected as principal driving factors for disease risk and progression. The increase in polystyrene nanoplastics in the environment from single-use plastics, recent detection of polystyrene contaminants in blood, and reports of anionic polystyrene… read more about Do the toxins of anionic nanoplastics have a possible role in Parkinson’s disease risk and progression? »

Malcolmson Lab Develops Catalytic Three Component Regiodivergent Reactions to Prepare Allylic Alkyl Amines

The Malcolmson lab has developed a three component carboamination of dienes utilizing aliphatic and aryl amines in conjunction with alkenyl electrophiles. Two different Pd-based catalysts allow for regiodivergent introduction of the amine reagent. The multicomponent coupling, together with the regiodivergence, enables the rapid production of a library of small molecule building blocks to facilitate drug discovery. Mechanistic experiments suggest the origin of regioselectivity with both catalysts, including a key pi-stacking… read more about Malcolmson Lab Develops Catalytic Three Component Regiodivergent Reactions to Prepare Allylic Alkyl Amines »

Embedding reactive bonds leads to less breakable materials

A study by the Craig lab and collaborators provides a blueprint for rewriting historical performance rules for materials made from polymer networks. Adding a small fraction of reactive groups in the right places within conventional networks can make the materials about 10 times more difficult to tear, and systematic studies uncover a physical picture at the heart of the phenomenon.  Read here for more information:  https://www.science.org/doi/full/10.1126/science.adg3229 read more about Embedding reactive bonds leads to less breakable materials »

Derbyshire Lab May Help Identify the Metabolite(s) Being Made by Parasites

How do parasites make natural products? A new study by the Derbyshire lab resolved a polyketide synthase present in Toxoplasma gondii and observed an unexpected self-acylation activity with acyl carrier proteins within this system. Their findings suggest a potential regulatory mechanism and may help identify the metabolite(s) being made by the parasite in future studies. You can read more about their work in a recent ACS Chemical Biology issue, available here. read more about Derbyshire Lab May Help Identify the Metabolite(s) Being Made by Parasites »

Derbyshire Lab investigates the activity of AT domains from the parasite Toxoplasma gondii

The Derbyshire lab has recently published a research article in Cell iScience investigating the activity of acyltransferase (AT) domains in a polyketide synthase from the apicomplexan parasite Toxoplasma gondii. Their work identifies a single amino acid in these domains responsible for protein activity which was able to be controlled through mutational studies, effectively serving as an "on-off" switch for AT activity.  Read more about their exciting work here! read more about Derbyshire Lab investigates the activity of AT domains from the parasite Toxoplasma gondii »

Coronavirus's Tangled Strands of RNA Could Offer New Ways to Treat People Who Get Infected

COVID19 cases are receding in some parts of the world but surging in other parts, especially those with limited access to vaccines, ultimately making the entire world population a vulnerable prey of the constantly emerging new variants. In a recent Science Advances publication, Martina Zafferani of the Hargrove Lab and collaborators tackled the problem by developing antivirals that take direct aim at SARS-CoV-2 RNA structure. They identified amiloride derivatives that can… read more about Coronavirus's Tangled Strands of RNA Could Offer New Ways to Treat People Who Get Infected »

Yokoyama and Yang Labs collaborate to find insights into the radical quenching step of radical SAM enzyme catalysis

A collaboration between the Yokoyama and Yang Labs has led to a publication of their latest work on the catalytic mechanism of MoaA radical SAM cyclase in molybdenum cofactor biosynthesis. In this work, combined efforts using electrochemistry, EPR spectroscopy, and DFT calculation provided evidence that the reduction of the aminyl radical intermediate proceeds by a proton-coupled electron transfer (PCET) with a 4Fe-4S cluster as an electron donor. The EPR also revealed an electronic coupling between GTP and… read more about Yokoyama and Yang Labs collaborate to find insights into the radical quenching step of radical SAM enzyme catalysis »