Linda J Roman studies how nitric oxide synthase (NOS) enzymes function and their impact on various health conditions. Specifically, she examines the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), which are important for brain function and blood vessel health, respectively. Her research includes developing drugs to inhibit nNOS for treating neurodegenerative diseases, understanding how gut bacteria in mice can affect health outcomes in medical research, and creating light-sensitive tools to activate eNOS for targeted therapies. This work is crucial for improving treatments for conditions like diabetes, cardiovascular diseases, and neurodegenerative disorders.
Key findings
Developed a light-sensitive trigger that is 20 times stronger at activating eNOS compared to earlier versions, aiding targeted cancer treatments.
Created modified compounds that are 13 times more effective at inhibiting nNOS, potentially improving therapies for Alzheimer's and Parkinson's diseases.
Demonstrated that different husbandry practices in mouse breeding can significantly alter gut microbiome diversity, critical for translating animal research to human health.
Frequently asked questions
Does Dr. Roman study neurodegenerative diseases?
Yes, she focuses on developing treatments for neurodegenerative diseases by targeting the neuronal nitric oxide synthase.
What is the significance of Dr. Roman's research on nitric oxide?
Her research is important because it helps improve treatments for conditions like heart disease and neurodegenerative disorders by better understanding how nitric oxide synthases function.
How does her work impact diabetes treatment?
Dr. Roman's studies on nNOS help enhance glucose uptake in muscle cells, offering insights for improving treatments for insulin resistance in diabetes patients.
What is the relevance of her research on gut microbiota?
Her findings show that housing conditions for laboratory mice can significantly impact their gut bacteria, which affects the outcomes of medical research using these animal models.
Is her work related to blood vessel health?
Yes, she researches endothelial nitric oxide synthase which is crucial for maintaining healthy blood flow and could lead to better treatments for cardiovascular conditions.
Publications in plain English
Effect of Husbandry Practices on the Fecal Microbiota of C57BL/6J Breeding Colonies Housed in 2 Different Barrier Facilities in the Same Institution.
2023
Journal of the American Association for Laboratory Animal Science : JAALAS
Roman LJ, Snijders AM, Chang H, Mao JH, Jones KJ +1 more
Plain English This study looked at how different care methods for mice affect the bacteria in their guts. Researchers found that mice raised in two different controlled environments had significant differences in their gut bacteria, which could impact their health and how they respond to treatments. Specifically, they discovered variations in gut microbiome diversity after just a few weeks of being housed in different conditions. This information is important because it helps improve the reliability of research using these mice as models for human health.
Who this helps: Patients and researchers who use mice in medical studies.
Design of Light-Sensitive Triggers for Endothelial NO-Synthase Activation.
2020
Antioxidants (Basel, Switzerland)
Dilly S, Roman LJ, Bogliotti N, Xie J, Deprez E +1 more
Plain English This study focused on creating light-sensitive tools to target and activate an enzyme called endothelial Nitric Oxide-Synthase (eNOS), which plays an important role in various cellular processes. Researchers developed new triggers that activate eNOS in response to laser light, with one specific trigger showing a 20-times stronger binding to the enzyme compared to earlier versions. This is significant because it could allow scientists to increase nitric oxide production where needed, which is helpful for understanding diseases or delivering targeted cancer treatments.
Who this helps: This benefits researchers working on cancer therapies and treatments for conditions related to blood vessel function.
Generation and characterization of functional phosphoserine-incorporated neuronal nitric oxide synthase holoenzyme.
2019
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
Zheng H, He J, Li J, Yang J, Kirk ML +2 more
Plain English The researchers focused on a specific form of a protein called neuronal nitric oxide synthase (nNOS), which is involved in producing nitric oxide in the brain. They developed a method to create an active version of this protein that includes a key modification (phosphoserine) at a specific spot, showing that the modified protein has similar functions to the regular one but with different electron transfer rates. This study is important because it provides a better way to explore how modifications to this protein affect its activity, which can help advance our understanding of brain signaling and potential treatments for related conditions.
Who this helps: This helps researchers and scientists studying brain function and diseases.
Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.
2017
Free radical biology & medicine
Kellogg DL, McCammon KM, Hinchee-Rodriguez KS, Adamo ML, Roman LJ
Plain English This study focused on how insulin and oxidative stress (like that caused by exercise) help muscles take in glucose, which is important for energy. The researchers found that a protein called neuronal nitric oxide synthase (nNOS) plays a key role in this process—when insulin or oxidative stress was present, nNOS activity increased, leading to greater glucose uptake. Specifically, when nNOS was blocked, glucose uptake dropped significantly, showing that it is essential for both insulin and oxidative stress responses in muscles.
Who this helps: This helps patients with insulin resistance, such as those with diabetes, by providing insights into ways to improve glucose uptake in their muscles.
Hydrophilic, Potent, and Selective 7-Substituted 2-Aminoquinolines as Improved Human Neuronal Nitric Oxide Synthase Inhibitors.
2017
Journal of medicinal chemistry
Pensa AV, Cinelli MA, Li H, Chreifi G, Mukherjee P +4 more
Plain English This study focused on developing new drugs to inhibit a specific enzyme called neuronal nitric oxide synthase (nNOS), which is important for treating neurodegenerative diseases. Researchers found that modified versions of a type of compound called 2-aminoquinolines were more effective at targeting nNOS in humans, showing significant improvements in their ability to inhibit this enzyme while minimizing interference with other brain targets. One key finding was that these new compounds improved selectivity and maintained a good ability to be absorbed by the body.
Who this helps: This benefits patients with neurodegenerative diseases by potentially leading to more effective treatments.
Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker.
2016
Journal of medicinal chemistry
Wang HY, Qin Y, Li H, Roman LJ, Martásek P +2 more
Plain English This study focused on developing new inhibitors that target a specific enzyme called neuronal nitric oxide synthase (nNOS), which is important for treating brain diseases. The researchers created a compound, known as Compound 14j, that is very effective at blocking this enzyme, showing a strength of 13 nanomolar for humans, which is significantly more effective than other similar compounds. This discovery matters because it could lead to better treatments for neurodegenerative disorders with fewer side effects.
Who this helps: Patients with neurodegenerative diseases.
Convergent synthesis and properties of photoactivable NADPH mimics targeting nitric oxide synthases.
2016
Organic & biomolecular chemistry
Nguyen NH, Bogliotti N, Chennoufi R, Henry E, Tauc P +5 more
Plain English This study focused on creating new compounds that mimic NADPH, a molecule important for producing nitric oxide in the body. The researchers found that these new compounds can light up under certain conditions, helping them bind to specific enzymes (nNOS and eNOS) that are crucial for blood vessel function. These findings are important because they open up possibilities for better targeting of treatments for conditions related to blood flow and heart health.
Who this helps: Patients with heart disease and related vascular conditions.
Instability of the Human Cytochrome P450 Reductase A287P Variant Is the Major Contributor to Its Antley-Bixler Syndrome-like Phenotype.
2016
The Journal of biological chemistry
McCammon KM, Panda SP, Xia C, Kim JJ, Moutinho D +8 more
Plain English Researchers studied a specific mutation in the NADPH-cytochrome P450 oxidoreductase gene, known as A287P, which causes serious health issues like skeletal deformities and sexual development problems. They found that this mutation makes the protein unstable, meaning it breaks down faster than the normal version, which is linked to the severe symptoms seen in patients. Specifically, A287P was shown to be less stable than the standard protein and degraded more quickly in cells, leading to a deficiency disorder.
Who this helps: This findings benefit patients with Antley-Bixler syndrome and related disorders by improving understanding of their condition.
Novel 2,4-disubstituted pyrimidines as potent, selective, and cell-permeable inhibitors of neuronal nitric oxide synthase.
2015
Journal of medicinal chemistry
Mukherjee P, Li H, Sevrioukova I, Chreifi G, Martásek P +3 more
Plain English This research focused on developing new drugs that specifically target a protein called neuronal nitric oxide synthase (nNOS), which is important for treating neurodegenerative diseases. The scientists created new compounds that were very effective at inhibiting this protein, achieving a potency of 13 times greater compared to previous drugs, and showed potential for being taken orally with low side effects. This research is significant because it could lead to better treatment options for conditions like Alzheimer's and Parkinson's, which involve nNOS.
Who this helps: Patients with neurodegenerative disorders.
Oxidative stress induces phosphorylation of neuronal NOS in cardiomyocytes through AMP-activated protein kinase (AMPK).
2015
Biochemical and biophysical research communications
Kar R, Kellogg DL, Roman LJ
Plain English This study investigated how oxidative stress affects a protein called neuronal nitric oxide synthase (nNOS) in heart cells (cardiomyocytes). Researchers found that short exposure to hydrogen peroxide (a type of oxidative stress) increased nNOS activity, which led to more nitric oxide production; specifically, the level of nNOS phosphorylation increased at a key site. However, longer exposure caused a decrease in nNOS, showing that timing matters in the way oxidative stress influences heart function.
Who this helps: This research benefits heart disease patients and doctors by improving understanding of how oxidative stress impacts heart cell function.
Probing the Hydrogen Bonding of the Ferrous-NO Heme Center of nNOS by Pulsed Electron Paramagnetic Resonance.
2015
The journal of physical chemistry. A
Astashkin AV, Chen L, Elmore BO, Kunwar D, Miao Y +4 more
Plain English This study looked at how the chemical structure of a specific area in a protein called neuronal nitric oxide synthase (nNOS) interacts with nitric oxide (NO), which is important for its function. The researchers found that when there is no substrate present, there isn’t any hydrogen bonding between the NO and surrounding water or the arginine substrate, unlike what previous studies suggested. However, when another compound (N-hydroxy-L-arginine) is present, it does form a hydrogen bond with the NO, meaning that its interactions change depending on what is present in the environment.
Who this helps: This research helps scientists and doctors understand how to better manipulate protein interactions in medical treatments involving nitric oxide.
2-Aminopyridines with a Truncated Side Chain To Improve Human Neuronal Nitric Oxide Synthase Inhibitory Potency and Selectivity.
2015
Journal of medicinal chemistry
Kang S, Li H, Tang W, Martásek P, Roman LJ +2 more
Plain English This study looked at new compounds designed to block a specific enzyme (nNOS), which plays a role in various brain functions. One of the compounds, called 19c, was found to be very effective, showing binding strengths of 24 nM for rat nNOS and 55 nM for human nNOS, while also being much more selective against other related enzymes. This matters because finding better inhibitors for nNOS could lead to improved treatments for conditions like neurodegenerative diseases or brain injuries.
Who this helps: Patients with neurological disorders.
Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase.
2015
Journal of medicinal chemistry
Cinelli MA, Li H, Pensa AV, Kang S, Roman LJ +3 more
Plain English The study focused on creating new compounds that can effectively inhibit a specific enzyme (nNOS) linked to neurodegenerative diseases by reducing excess nitric oxide in the brain. The researchers developed a compound that showed strong effectiveness (high potency) against nNOS and minimized unwanted interactions with other receptors. Specifically, the most promising compound demonstrated a good balance of effectiveness and the ability to cross into the brain, which is crucial for treating neurological conditions.
Who this helps: This helps patients with neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
Potent and selective double-headed thiophene-2-carboximidamide inhibitors of neuronal nitric oxide synthase for the treatment of melanoma.
2014
Journal of medicinal chemistry
Huang H, Li H, Yang S, Chreifi G, Martásek P +4 more
Plain English Researchers studied new compounds that can block a specific enzyme called neuronal nitric oxide synthase (nNOS), which may be important for treating melanoma, a type of skin cancer. They found that two of these compounds, labeled 13 and 14, are very effective, with a strength measure showing that they can inhibit nNOS at just 5 nanomoles, and they target nNOS much more effectively than similar enzymes (440- to 540-fold more selective). This is significant because it could lead to better treatment options for melanoma patients by specifically targeting harmful cells without affecting healthy ones.
Who this helps: Patients with melanoma.
Simplified 2-aminoquinoline-based scaffold for potent and selective neuronal nitric oxide synthase inhibition.
2014
Journal of medicinal chemistry
Cinelli MA, Li H, Chreifi G, Martásek P, Roman LJ +2 more
Plain English Researchers developed new chemical compounds based on a structure called 2-aminoquinoline to target an enzyme linked to neurodegenerative diseases. They found that some of these compounds effectively block neuronal nitric oxide synthase (nNOS) without affecting other related enzymes, with the best-performing compounds showing strong action and good potential for oral delivery. This is important because lowering nitric oxide levels in the brain might help treat conditions like Alzheimer's and Parkinson's.
Who this helps: This helps patients with neurodegenerative diseases.
Deciphering the binding of caveolin-1 to client protein endothelial nitric-oxide synthase (eNOS): scaffolding subdomain identification, interaction modeling, and biological significance.
2014
The Journal of biological chemistry
Trane AE, Pavlov D, Sharma A, Saqib U, Lau K +4 more
Plain English This study looked at how a protein called caveolin-1 (Cav-1) interacts with another protein, endothelial nitric-oxide synthase (eNOS), which is important for blood vessel function. The researchers found that a specific part of the Cav-1 protein (amino acids 90-99) is crucial for its interaction with eNOS and that a mutation in Cav-1 can actually increase the production of nitric oxide, which helps keep blood vessels open. This is important because understanding this interaction could lead to new ways to improve blood flow in people with cardiovascular issues.
Who this helps: This helps patients with cardiovascular diseases.
An Accessible Chiral Linker to Enhance Potency and Selectivity of Neuronal Nitric Oxide Synthase Inhibitors.
2014
ACS medicinal chemistry letters
Jing Q, Li H, Roman LJ, Martásek P, Poulos TL +1 more
Plain English This study focused on developing new compounds that specifically inhibit a type of enzyme called neuronal nitric oxide synthase (nNOS), which is important for treating conditions like neurodegenerative diseases. The researchers created eight new compounds, with one showing particularly strong effects: it had a potency of 9.7 nanomolar and was highly selective against two other similar enzymes, making it a promising candidate for further research. This matters because improving selectivity can help reduce side effects and enhance the efficacy of treatments for diseases affecting the nervous system.
Who this helps: This benefits patients with neurodegenerative diseases.
Nitric oxide synthase inhibitors that interact with both heme propionate and tetrahydrobiopterin show high isoform selectivity.
2014
Journal of medicinal chemistry
Kang S, Tang W, Li H, Chreifi G, Martásek P +3 more
Plain English This study looked at new compounds that can specifically block a form of an enzyme called nNOS, which produces nitric oxide and is linked to various nerve disorders. The researchers found that one compound, called 8R, was the most effective, blocking nNOS with a strong potency of 24 nanomolar and showing much higher selectivity against other forms of the enzyme (iNOS and eNOS), making it 273 times and over 2800 times less likely to affect those other forms, respectively. This is important because it could lead to safer treatments for nerve-related conditions while reducing unwanted side effects.
Who this helps: Patients with neuronal disorders.
Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase.
2014
Bioorganic & medicinal chemistry letters
Jing Q, Li H, Roman LJ, Martásek P, Poulos TL +1 more
Plain English This study focused on creating new drugs that can effectively block a specific enzyme called neuronal nitric oxide synthase (nNOS), which is important for brain function. Researchers developed a new type of molecule called (S)-9b, which is very powerful at inhibiting nNOS, showing a strength of 14.7 nM, and is over 1,100 times more selective for nNOS compared to related enzymes (eNOS and iNOS). This is significant because it could lead to better treatments for conditions related to brain function without affecting other systems in the body.
Who this helps: This research benefits patients with neurological disorders that involve nNOS.
Holoenzyme structures of endothelial nitric oxide synthase - an allosteric role for calmodulin in pivoting the FMN domain for electron transfer.
2014
Journal of structural biology
Volkmann N, Martásek P, Roman LJ, Xu XP, Page C +3 more
Plain English This study looked at the detailed structure of an important enzyme called endothelial nitric oxide synthase (eNOS), specifically how it interacts with a molecule called calmodulin. Researchers found that calmodulin helps the enzyme work better by stabilizing its structure and allowing parts of it to move more efficiently, which is critical for producing nitric oxide, a substance that helps blood vessels relax. This knowledge is important because a better understanding of how eNOS functions can lead to improved treatments for conditions related to blood vessel health.
Who this helps: This helps patients with cardiovascular conditions by informing potential treatments.
Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase.
2013
Bioorganic & medicinal chemistry
Li H, Xue F, Kraus JM, Ji H, Labby KJ +6 more
Plain English This study looked at new chemical compounds designed to block a specific enzyme involved in brain function, potentially helping with neurological disorders. The researchers created several variants of these compounds and found that three of them were effective at very low concentrations, specifically showing strong inhibition with concentrations in the double-digit nanomolar range. Understanding how these inhibitors work is important for developing better treatments for conditions like Alzheimer's or other neurological issues.
Who this helps: This research benefits patients with neurological disorders and the doctors treating them.
Structure-guided design of selective inhibitors of neuronal nitric oxide synthase.
2013
Journal of medicinal chemistry
Huang H, Li H, Martásek P, Roman LJ, Poulos TL +1 more
Plain English This study focused on creating a specific drug that blocks a type of enzyme called neuronal nitric oxide synthase (nNOS), which is important in brain function and can be involved in neurodegenerative diseases. The researchers developed an inhibitor, referred to as compound 7, which was found to be very effective, blocking nNOS at very low doses (nanomolar levels) and was 472 times more selective for nNOS compared to another type of enzyme (eNOS). This is important because a selective inhibitor could potentially lead to better treatments for brain diseases without affecting other enzymes that have different functions.
Who this helps: This benefits patients with neurodegenerative diseases by potentially providing more targeted treatments.
Methylated N(ω)-hydroxy-L-arginine analogues as mechanistic probes for the second step of the nitric oxide synthase-catalyzed reaction.
2013
Biochemistry
Jansen Labby K, Li H, Roman LJ, Martásek P, Poulos TL +1 more
Plain English This study focused on how the enzyme nitric oxide synthase (NOS) converts a molecule called L-arginine into other substances, which is important for various body functions, including signaling between cells. The researchers created different versions of a key molecule involved in this process and found that one of their new versions, N(ω)-methoxy-L-arginine, successfully produced important byproducts, including citrulline and nitric oxide. This research helps unveil how NOS works at a detailed level, which is crucial for understanding diseases tied to nitric oxide production.
Who this helps: This benefits researchers studying nitric oxide's role in diseases and developing new treatments.
Sestrin 2 and AMPK connect hyperglycemia to Nox4-dependent endothelial nitric oxide synthase uncoupling and matrix protein expression.
2013
Molecular and cellular biology
Eid AA, Lee DY, Roman LJ, Khazim K, Gorin Y
Plain English This study looked at how high blood sugar levels, common in diabetes, harm kidney cells by disrupting a critical enzyme responsible for producing nitric oxide, which helps keep blood vessels healthy. The researchers found that a protein called Nox4 increases harmful molecules in these cells when exposed to high glucose, leading to damage. When they activated a protective pathway involving another protein called sestrin 2, they could reduce this damage and prevent excess fibronectin, which contributes to kidney dysfunction.
Who this helps: Patients with diabetes and kidney problems.
In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.
2013
Bioorganic & medicinal chemistry
Jing Q, Li H, Fang J, Roman LJ, Martásek P +2 more
Plain English This study focused on finding new drugs that can effectively block a specific enzyme, called neuronal nitric oxide synthase (nNOS), which produces harmful levels of nitric oxide in certain brain diseases. Researchers created new compounds that are easier to make and work better in the body than previous drug candidates, achieving promising results in early tests. This is important because it could lead to better treatments for neurodegenerative diseases without affecting the important functions of other related enzymes.
Who this helps: Patients with neurodegenerative diseases.
Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: role of mitochondrial reactive oxygen species.
2013
The Journal of biological chemistry
Lee DY, Wauquier F, Eid AA, Roman LJ, Ghosh-Choudhury G +3 more
Plain English This study looked at how a hormone called angiotensin II affects certain cells in the kidneys, leading to damage in the blood vessels. Researchers found that angiotensin II causes a specific enzyme (eNOS) to malfunction, which leads to less production of nitric oxide, a substance that helps keep blood vessels healthy. They discovered that a protein called Nox4 plays a key role in this process by increasing harmful reactive oxygen species, which contributes to the buildup of fibronectin, a protein that can lead to kidney damage if produced in excess.
Who this helps: Patients with kidney disease who are at risk of further damage.
Chiral linkers to improve selectivity of double-headed neuronal nitric oxide synthase inhibitors.
2013
Bioorganic & medicinal chemistry letters
Jing Q, Li H, Chreifi G, Roman LJ, Martásek P +2 more
Plain English Researchers created new compounds to specifically target a type of enzyme called neuronal nitric oxide synthase (nNOS), which plays a role in brain functions. One of the compounds they tested, labeled (R)-6b, was found to be very effective, working at a concentration of 32 nanomoles per liter and being 475 times more selective for nNOS than another related enzyme, endothelial nitric oxide synthase (eNOS). This study highlights how the specific arrangement of atoms in these compounds affects their ability to inhibit nNOS, which could lead to better treatments for illnesses linked to nitric oxide production in the brain.
Who this helps: This research benefits patients with neurological conditions related to nitric oxide.
Intra- and inter-molecular effects of a conserved arginine residue of neuronal and inducible nitric oxide synthases on FMN and calmodulin binding.
2013
Archives of biochemistry and biophysics
Panda SP, Polusani SR, Kellogg DL, Venkatakrishnan P, Roman MG +3 more
Plain English This study examined how a specific amino acid, arginine, affects the binding of a protein called calmodulin (CaM) to nitric oxide synthases (NOSs), which are enzymes responsible for producing a signaling molecule called nitric oxide (NO). Researchers found that changing this arginine to another amino acid reduced the ability of NOSs to bind to CaM by about three times and decreased their ability to bind another molecule, FMN, by 20% to 60%. Understanding these interactions is important because they impact how effectively NOSs produce NO, which plays a critical role in various bodily functions.
Who this helps: This information benefits researchers and doctors who are working on treatments related to nitric oxide and its signaling pathways in health and disease.
Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle.
2013
Biochemical and biophysical research communications
Hinchee-Rodriguez K, Garg N, Venkatakrishnan P, Roman MG, Adamo ML +2 more
Plain English This study looked at how insulin affects a specific enzyme called neuronal nitric oxide synthase (nNOS) in skeletal muscle, which is important for glucose uptake. The researchers found that when insulin is given, nNOS is quickly modified (or phosphorylated), leading to an increase in nitric oxide production, which is crucial for how muscles use glucose. This is significant because understanding this process can help us find better ways to treat or prevent Type 2 Diabetes, where insulin’s effectiveness is reduced.
Who this helps: This benefits patients with Type 2 Diabetes and healthcare providers looking for new treatment strategies.
Conditional deletion of cytochrome p450 reductase in osteoprogenitor cells affects long bone and skull development in mice recapitulating antley-bixler syndrome: role of a redox enzyme in development.
2013
PloS one
Panda SP, Guntur AR, Polusani SR, Fajardo RJ, Gakunga PT +2 more
Plain English This study explored the role of a specific enzyme called POR in bone development by creating a special type of mouse that lacks this enzyme in certain bone-forming cells. The researchers found that these mice were smaller and had serious issues with their skull and long bones, including a premature fusion of skull bones and shorter long bones, with a decrease in bone density. This is significant as it helps understand how mutations in POR can lead to severe bone and facial deformities in humans, similar to those seen in Antley-Bixler syndrome.
Who this helps: This helps patients with Antley-Bixler syndrome and doctors working with them.
Differential calmodulin-modulatory and electron transfer properties of neuronal nitric oxide synthase mu compared to the alpha variant.
2013
FEBS letters
Panda SP, Li W, Venkatakrishnan P, Chen L, Astashkin AV +3 more
Plain English This study examined two types of a brain enzyme called neuronal nitric oxide synthase, focusing on how their structures affect how they transfer electrons and are regulated by a molecule called calmodulin. They found that the mu variant of this enzyme was quicker at transferring electrons when calmodulin wasn't present, but overall, it reacted slower in its interaction with calmodulin compared to the alpha variant. This is important because it helps scientists understand the differences in enzyme behavior, which can influence how cells communicate and respond under certain conditions.
Who this helps: This helps researchers and doctors studying brain functions and developing treatments for related conditions.
Intramolecular hydrogen bonding: a potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase.
2012
Bioorganic & medicinal chemistry
Labby KJ, Xue F, Kraus JM, Ji H, Mataka J +5 more
Plain English This study looked at new types of drugs designed to better target a specific enzyme involved in neurodegenerative diseases, which can be harder to treat. Researchers found that two of the new drugs worked better at entering cells than older versions, showing an increase in effectiveness. This matters because improving how well these drugs can get into cells could lead to better treatments for conditions like Alzheimer's and Parkinson's.
Who this helps: Patients with neurodegenerative diseases.
Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations.
2012
Journal of the American Chemical Society
Huang H, Ji H, Li H, Jing Q, Labby KJ +4 more
Plain English This study focused on developing new drugs that can effectively inhibit a specific enzyme linked to neurodegenerative diseases, which may reduce harmful levels of nitric oxide in the brain. The researchers created a series of new compounds and found that some of these, particularly one labeled as "10," are very effective at doing this while also being able to enter cells better than previous versions. This matters because it could lead to better treatment options for mental health and neurodegenerative conditions.
Who this helps: This helps patients with neurodegenerative diseases and their doctors.
Nitric oxide synthases activation and inhibition by metallacarborane-cluster-based isoform-specific affectors.
2012
Journal of medicinal chemistry
Kaplánek R, Martásek P, Grüner B, Panda S, Rak J +3 more
Plain English This study looked at new compounds made from boron clusters to see how they could activate or inhibit different versions of an enzyme called nitric oxide synthase. The researchers found that some of these compounds effectively blocked nitric oxide production, with varying success across the three types of this enzyme. This matters because controlling nitric oxide levels can help treat various health conditions related to circulation and inflammation.
Who this helps: This helps patients who need better treatments for conditions related to blood flow and inflammation.
Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase.
2011
Journal of medicinal chemistry
Xue F, Fang J, Delker SL, Li H, Martásek P +3 more
Plain English This study explored new drugs designed to inhibit a specific enzyme in the brain called neuronal nitric oxide synthase (nNOS). The best new drug, named 3j, was found to be very effective at very low doses and easily passes through cell membranes, which is important for treatment. The findings could lead to better treatments for conditions like cerebral palsy by providing targeted inhibition of nNOS while sparing other similar enzymes.
Who this helps: Patients with neurological conditions such as cerebral palsy.
Improved synthesis of chiral pyrrolidine inhibitors and their binding properties to neuronal nitric oxide synthase.
2011
Journal of medicinal chemistry
Xue F, Kraus JM, Labby KJ, Ji H, Mataka J +7 more
Plain English Researchers created a new way to make special compounds called chiral pyrrolidine inhibitors, aimed at a specific enzyme in the brain known as neuronal nitric oxide synthase (nNOS). They successfully tested five new versions of these inhibitors and found that adding fluorine atoms improved how well they bind to nNOS. This work is important for developing better treatments for conditions related to nNOS, which plays a role in various neurological disorders.
Who this helps: Patients with neurological disorders.
Potent and selective neuronal nitric oxide synthase inhibitors with improved cellular permeability.
2010
Bioorganic & medicinal chemistry letters
Xue F, Fang J, Lewis WW, Martásek P, Roman LJ +1 more
Plain English Researchers studied new compounds designed to effectively block a specific enzyme related to brain function, known as neuronal nitric oxide synthase. They created three versions that included changes to improve how well these compounds could enter cells. The two most promising versions maintained their strong effects while also being better at passing through cell membranes, which is crucial for their success in medical applications.
Who this helps: This research helps patients with neurological conditions by potentially leading to better treatments.
Heme-coordinating inhibitors of neuronal nitric oxide synthase. Iron-thioether coordination is stabilized by hydrophobic contacts without increased inhibitor potency.
2010
Journal of the American Chemical Society
Martell JD, Li H, Doukov T, Martásek P, Roman LJ +3 more
Plain English This study explored a new type of inhibitor designed to affect a specific enzyme in the brain called neuronal nitric oxide synthase (nNOS), which is involved in various neurological processes. Researchers created and tested several thioether-based inhibitors and found that while these inhibitors bind to nNOS, they do not increase their effectiveness as previously thought. Specifically, they discovered that the connection between the thioether and heme iron is weaker than expected, which affects how well the inhibitors work.
Who this helps: This research benefits scientists developing treatments for neurological disorders.
Structure-based design, synthesis, and biological evaluation of lipophilic-tailed monocationic inhibitors of neuronal nitric oxide synthase.
2010
Bioorganic & medicinal chemistry
Xue F, Huang J, Ji H, Fang J, Li H +4 more
Plain English This study investigated new compounds that could inhibit an enzyme called neuronal nitric oxide synthase (nNOS), which is important in neurodegenerative diseases. The researchers designed and tested several new compounds but found that they were not very effective; they showed low potency because their structure didn't interact properly with nNOS. Understanding how these compounds work — or don’t work — helps improve the design of future treatments for neurodegenerative diseases.
Who this helps: This helps researchers developing new drugs for patients with neurodegenerative conditions.
Peripheral but crucial: a hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) for potent and selective inhibition of neuronal nitric oxide synthase.
2010
Bioorganic & medicinal chemistry letters
Xue F, Li H, Fang J, Roman LJ, Martásek P +2 more
Plain English This study looked at how to create new drugs that can specifically block the neuronal nitric oxide synthase (nNOS) enzyme, which is important in treating neurodegenerative diseases, without affecting other similar enzymes. Researchers found that certain chemical compounds (2a and 3) can effectively bind to a specific area on the enzyme, making them potent and selective inhibitors. This discovery is important because it could lead to better treatments for conditions like Alzheimer's disease by targeting nNOS specifically.
Who this helps: This helps patients with neurodegenerative diseases.
Potent, highly selective, and orally bioavailable gem-difluorinated monocationic inhibitors of neuronal nitric oxide synthase.
2010
Journal of the American Chemical Society
Xue F, Li H, Delker SL, Fang J, Martásek P +3 more
Plain English This study focused on developing new drugs to specifically inhibit a brain enzyme called neuronal nitric oxide synthase (nNOS) that is involved in various neurological functions. Researchers created new compounds that showed a strong ability to block nNOS, with one compound being particularly effective at a concentration of 36 nanomolar, which is 3800 times more selective for nNOS compared to another enzyme, eNOS. This work is important because having a highly selective and effective nNOS inhibitor could lead to better treatments for conditions related to brain function and could have fewer side effects.
Who this helps: Patients with neurological disorders.
Hypoadiponectinemia is closely associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects.
2010
Metabolic syndrome and related disorders
Kashyap SR, Roman LJ, Mandarino L, DeFronzo R, Bajaj M
Plain English This study looked at how a protein called adiponectin affects the activity of nitric oxide synthase (NOS) in the muscles of people with type 2 diabetes compared to those without diabetes. Researchers found that people with type 2 diabetes had significantly lower levels of plasma adiponectin (4.5 micrograms/mL) compared to controls (7.0 micrograms/mL) and showed less improvement in NOS activity after insulin stimulation. These results indicate that lower adiponectin levels are linked to worse muscle function and insulin resistance in type 2 diabetes, potentially increasing the risk of heart disease and related complications.
Who this helps: This research benefits patients with type 2 diabetes by highlighting a potential target for improving their muscle function and cardiovascular health.
Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives.
2010
Journal of medicinal chemistry
Ji H, Delker SL, Li H, Martásek P, Roman LJ +2 more
Plain English This study focused on developing and testing new compounds that inhibit a brain enzyme called neuronal nitric oxide synthase (nNOS), which is important for preventing brain injury and treating neurodegenerative diseases. Researchers found two promising inhibitors with extraordinary effectiveness—over 1000 times more selective for nNOS than a similar enzyme called eNOS. These findings matter because they could lead to better treatments for conditions like Alzheimer’s or Parkinson’s disease by targeting specific brain processes involved in these disorders.
Who this helps: This helps patients with neurodegenerative diseases.
Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping.
2009
Journal of medicinal chemistry
Ji H, Li H, Martásek P, Roman LJ, Poulos TL +1 more
Plain English This study focused on developing new drugs to block a brain enzyme called neuronal nitric oxide synthase (nNOS), which can help prevent brain injuries and treat neurodegenerative diseases. Researchers created 20 new drug candidates that were not only more effective at inhibiting nNOS but also had better properties for use as medications, showing significant improvement in their ability to work just like drugs should. This is important because having better options for treating brain-related conditions can lead to improved patient outcomes.
Who this helps: Patients with neurodegenerative diseases and brain injuries.
Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy.
2009
Annals of neurology
Ji H, Tan S, Igarashi J, Li H, Derrick M +5 more
Plain English This study focused on developing new drugs that could prevent cerebral palsy (CP) by targeting a specific brain enzyme in rabbits. The researchers found that by using these new drugs, they could significantly reduce deaths and the number of newborn rabbits showing signs of CP, with a notable improvement in survival rates and neurological health. This research is important because it may lead to effective prevention methods for CP in humans.
Who this helps: This helps expectant mothers and healthcare providers by offering new potential treatments to reduce the risk of cerebral palsy in newborns.
Analogues of 2-aminopyridine-based selective inhibitors of neuronal nitric oxide synthase with increased bioavailability.
2009
Bioorganic & medicinal chemistry
Lawton GR, Ralay Ranaivo H, Chico LK, Ji H, Xue F +4 more
Plain English This research focused on improving a specific drug that inhibits an enzyme called neuronal nitric oxide synthase (nNOS), which is linked to brain diseases. The scientists modified the drug to make it easier for the body to absorb, finding that a new version of the compound could still effectively block nNOS while being better at getting into the brain. The improved drug is likely to be more effective in treating neurodegenerative conditions.
Who this helps: This benefits patients with neurodegenerative diseases.
L337H mutant of rat neuronal nitric oxide synthase resembles human neuronal nitric oxide synthase toward inhibitors.
2009
Journal of medicinal chemistry
Fang J, Ji H, Lawton GR, Xue F, Roman LJ +1 more
Plain English This study examined how a specific change in a rat enzyme (by altering one part of its structure) makes it behave more like the human version of that enzyme. The researchers found that by changing Leu-337 to His in the rat neuronal nitric oxide synthase (nNOS), the enzyme's characteristics closely align with those of human nNOS. This finding is important because it can help streamline the design and development of new drugs that target human enzymes more effectively.
Who this helps: This helps drug developers and researchers working on treatments for conditions related to the nervous system.
Synthesis and enzymatic evaluation of 2- and 4-aminothiazole-based inhibitors of neuronal nitric oxide synthase.
2009
Beilstein journal of organic chemistry
Lawton GR, Ji H, Martásek P, Roman LJ, Silverman RB
Plain English Researchers created and tested new drugs that block a specific brain enzyme called neuronal nitric oxide synthase (nNOS) to see if they could effectively treat conditions related to the brain. They found that a new drug with a 2-aminothiazole part was weaker than a previous version with a different structure, and that another variation, 4-aminothiazole, broke down quickly in water and lost its effectiveness. Understanding how these different structures affect the drugs' performance is crucial for developing better treatments for brain conditions.
Who this helps: Patients with neurological disorders.
Deletion of the autoregulatory insert modulates intraprotein electron transfer in rat neuronal nitric oxide synthase.
2008
FEBS letters
Feng C, Roman LJ, Hazzard JT, Ghosh DK, Tollin G +1 more
Plain English This study looked at how removing a specific part of a protein in rats affects the way electrons move within that protein. The researchers found that while the movement of electrons slowed down by two to three times in the modified protein, the speed at which electrons are processed remained unchanged. This is important because it suggests that the removed part helps stabilize the output of the electron transfer, which could have implications for understanding how these proteins function in the body.
Who this helps: This helps researchers studying brain function and related health conditions.