Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, 2024 Bridgewater College
Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, Matthew Ellis
Honors Projects
This research investigates the synthesis of α-chloro-β-lactone molecules, focusing on the production, isolation, and purification of two precursor compounds from chloroacetic acid and substituted benzaldehydes. While multiple methods were explored, including EDC, DIC, and DCC catalysis, DCC proved to be most effective in producing higher yields. However, challenges in purification arose due to the formation of byproducts, particularly with DCC, prompting further investigation for efficient extraction and purification techniques. DCC, however, shows a promising route for α-chloro-β-lactone synthesis, despite purification complexities.
Modern Approaches To Treating Hospital Acquired Infections: An Overview Of Current Treatments Using Antibiotics And New Therapies Centered Around Photo-Activated Porphyrins, 2024 Liberty University
Modern Approaches To Treating Hospital Acquired Infections: An Overview Of Current Treatments Using Antibiotics And New Therapies Centered Around Photo-Activated Porphyrins, Meghan Johns
Senior Honors Theses
Annually, hospital-acquired infections (HAIs) affect hundreds of thousands of people in the U.S. and impose a great economic burden. The current problem is further exacerbated due to the failure of traditional treatment strategies considering the rise in antimicrobial resistance rates. Besides the fact that antimicrobial resistances complicates clinical treatment strategies, patients are also more vulnerable to secondary infections and complications from prolonged antibiotic use. As a result, research investigating novel treatment strategies for bacterial infections has recently increased. A strategy using porphyrin-based compounds is showing promise. Porphyrins and their derivatives have exhibited bactericidal effects against Gram-positive bacteria by the destruction …
Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, 2024 ShanghaiTech University
Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai
Mathematics, Physics, and Computer Science Faculty Articles and Research
The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …
Computer Aided Design Of Aromatic Foldamer Targeting Protein-Protein Interaction, 2024 Rowan University
Computer Aided Design Of Aromatic Foldamer Targeting Protein-Protein Interaction, Bamidele Towolawi
Graduate Student and Postdoctoral Fellow Symposium
With the computational tools developed in our lab for accurate prediction of structures and solution dynamics of aromatic foldamers, we now target protein-protein interaction (PPI) by appending proteinogenic side chains on the external surfaces of the helical aromatic foldamers. Particularly, the activation of a regulatory protein NF-κB, a key player in the inflammatory response and cell proliferation, involves binding of NEMO (NF-κB Essential Modulator) with linear di-ubiquitin. In this study, we designed various sequences based on established protocols and investigated, by utilizing molecular dynamics (MD) simulations, their potential binding to di-ubiquitin, specifically targeting the NEMO binding interface. This study complements …
Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, 2024 The Ohio State University
Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …
Novel Inhibitors To Mmpl3 Transporter Of Mycobacterium Tuberculosis By Structure-Based High-Throughput Virtual Screening And Molecular Dynamics Simulations, 2024 Rowan University
Novel Inhibitors To Mmpl3 Transporter Of Mycobacterium Tuberculosis By Structure-Based High-Throughput Virtual Screening And Molecular Dynamics Simulations, Hetanshi Choksi, Justin Carbone, Nicholas J. Paradis, Lucas Bennett, Candice Bui-Linh, Chun Wu
Faculty Scholarship for the College of Science & Mathematics
Tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis (Mtb) utilizes mycolic acids for building the mycobacterial cell wall, which is critical in providing defense against external factors and resisting antibiotic action. MmpL3 is a secondary resistance nodulation division transporter that facilitates the coupled transport of mycolic acid precursor into the periplasm using the proton motive force, thus making it an attractive drug target for TB infection. In 2019, X-ray crystal structures of MmpL3 from M. smegmatis were solved with a promising inhibitor SQ109, which showed promise against drug-resistant TB in Phase II clinical trials. Still, there is a pressing need to discover more …
Development Of Salinomycin Derivatives As Potential Anticancer Agents, 2024 Rowan University
Development Of Salinomycin Derivatives As Potential Anticancer Agents, Viren Soni
Theses and Dissertations
Salinomycin is a poly-ionophore antibiotic that was originally isolated from Streptomyces albus by Miyazaki and colleagues from Kaken Chemicals Co., Ltd., Tokyo, Japan. Salinomycin exhibits antimicrobial activity against Gram-positive bacteria including Bacillus subtilis, Staphylococcus aureus, Micrococcus flavus, Sarcina lutea, Mycobacterium spp. Some filamentous fungi, Plasmodium falciparum, and Eimeria spp. as well as protozoan parasites responsible for the poultry disease coccidiosis. Hence, it is used in veterinary medicine. In 2009 Gupta et al demonstrated that salinomycin selectively killed human breast cancer stem cells (CSCs) with great efficacy, and the mechanism of action of this novel CSCs molecule was explored. To name …
Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, 2024 Bridgewater College
Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, Matthew Ellis
ASPIRE 2024
This research investigates the synthesis of α-chloro-β-lactone molecules, focusing on the production, isolation, and purification of two precursor compounds from chloroacetic acid and substituted benzaldehydes. While multiple methods were explored, including EDC, DIC, and DCC catalysis, DCC proved to be most effective in producing higher yields. However, challenges in purification arose due to the formation of byproducts, particularly with DCC, prompting further investigation for efficient extraction and purification techniques. DCC, however, shows a promising route for α-chloro-β-lactone synthesis, despite purification complexities.
De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, 2024 Chapman University
De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …
Analyzing Novel Metal Alloys For Glucose Sensing And Electrocatalysis, 2024 Rowan University
Analyzing Novel Metal Alloys For Glucose Sensing And Electrocatalysis, Anna Grace Boddy
Theses and Dissertations
In pharmaceutical and medicinal chemistry, metals and metal alloys often receive less attention compared to biological or organic compounds due to many factors including toxicity in the body for drug development or the cost of these metals. However, metals can play an important role in pharmaceuticals, having an impact on original cancer drugs, such as platinum used for head and neck tumors. Electrocatalysis is also another topic that receives less attention over topics such as chromatography in pharmaceuticals due to its potential toxic catalysts and voltages that could be harmful to the body. Electrocatalytic sensors can play an important role …
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, 2024 Old Dominion University
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal
Chemistry & Biochemistry Faculty Publications
Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …
Covalent Inhibition Of Enzyme Sortase A As A New Pathway Against Bacterial Resistance Of Staphylococcus Aureus, 2023 University of San Francisco
Covalent Inhibition Of Enzyme Sortase A As A New Pathway Against Bacterial Resistance Of Staphylococcus Aureus, Umyeena Bashir
Master's Theses
The continued rise of antibiotic-resistant bacteria, such as MRSA (methicillin-resistant Staphylococcus aureus), has made the discovery of novel antibiotics critical. While bacteriostatic and bactericidal antibiotics inevitably exert evolutionary pressure on bacteria to develop resistance, small molecules that target mechanisms of bacterial virulence present a promising alternative for treatment. Sortase A (Srt A), a cysteine protease of S. aureus, promotes bacterial virulence by covalently attaching proteins such as pilin to the bacterial surface, enabling bacterial adhesion to mammalian cells. Inhibitory studies of this enzyme have gained prominent interest as a new pathway for drug development since blocking this enzyme's ability to …
Achieving Warranted Acceptance Of Biotechnologies, 2023 Carnegie Mellon University
Achieving Warranted Acceptance Of Biotechnologies, Emily Grayek, Baruch Fischhoff
Level 3
The U.S. has faced long-standing shortages of generic drugs, causing negative health effects and spikes in drug costs. To address these shortages, investments in critical technologies and policies to support their adoption will be needed. The success of these technologies and policies depends on public acceptance. We studied public acceptance using the mental model approach, which identifies gaps in understanding that can be addressed with communications. We began with semi-structured interviews with experts in pharmaceutical manufacturing. Based on these interviews, we developed and conducted surveys of the general public, physicians, and pharmacists. Similar strategies could be applied to improve communications …
Valerie Mulholland On Improving Rbdm Effectiveness, 2023 GMP Training & Pharmaceutical Regulatory Science Team (PRST), TU Dublin, Ireland
Valerie Mulholland On Improving Rbdm Effectiveness, Valerie Mulholland
Level 3
No abstract provided.
Agenda From June 1st Conference, 2023 Technological University Dublin
Speaker Bios, 2023 Technological University Dublin
Ipq Descriptor, 2023 Technological University Dublin
Hpra’S Kevin O’Donnell On The Ich Q9 Revision And Considerations For Its Implementation, 2023 Health Product Regulatory Authority, Ireland
Hpra’S Kevin O’Donnell On The Ich Q9 Revision And Considerations For Its Implementation, Kevin O'Donnell
Level 3
At the June 2023 PRST meeting on the ICH Q9 revision, HPRA Market Compliance Manager and Senior GMP Inspector Kevin O’Donnell, who has been serving as rapporteur for ICH Q9 (R1), addressed the changes introduced in the revision, the practicalities of implementation, and his “personal thoughts” on the implementation process. Click here for ICH Q9(R1) with the changes highlighted by O’Donnell, and here for the slides accompanying O’Donnell’s remarks. Formatting
changes and other minor edits have been made for clarity by IPQ. Expressions of thanks to the meeting organizers/attendees and disclaimers that the presentation represents the speaker’s views and not …
Balancing Quality Assurance & Innovation In Pharma, 2023 Pharmaceutical Regulatory Science Team (PRST)
Balancing Quality Assurance & Innovation In Pharma, Emma Ramnarine
Level 3
At the Pharmaceutical Regulatory Science Team (PRST) workshop on ICH Q9(R1), held at the Technological University Dublin in early June 2023, Boehringer Ingelheim US Biopharma Operations Product Management & Development Operations Head Emma Ramnarine shared her insights on balancing quality assurance and innovation in pharmaceutical manufacturing. She addressed: ● patient-centered transformation ● a watershed moment in her career ● understanding the drug shortage problem ● disruptive collaboration, and ● systems thinking
approaches. Click here for the slides accompanying Ramnarine’s remarks. She connected some of her remarks for the pharmaceutical industry to those made in the previous talk by Ed Hoffman, …
Quality Reborn, 2023 Quality Business Administration
Quality Reborn, Anders Vinther
Level 3
It is time for Quality leaders to not only fulfill the traditional role of ensuring cGMP compliance within the company but also take the Quality profession to the level of business leadership like Deming did in Japan after World War II. FDA has recently stated that they have low confidence in quality management maturity of the pharmaceutical industry.
For quality leaders to also become good business leaders we must educate them in ways that are different from what we currently do. The education should be in the 6 areas
- Visibly Demonstrating Responsibility of Quality
- Risk-Informed Decision Making and Communication
- Engaging …