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Articles 1 - 30 of 573

Full-Text Articles in Medicinal and Pharmaceutical Chemistry

Behavioral Analysis Of Conditions And Treatments Affecting Movement And Nociception, Indu Mithra Madhuranthakam Jun 2021

Behavioral Analysis Of Conditions And Treatments Affecting Movement And Nociception, Indu Mithra Madhuranthakam

Theses and Dissertations

This thesis work includes three projects. First part deals with the investigation of novel D2 receptor ligands in Prepulse inhibition. The goal of this study is to establish a relationship between dopamine receptor antagonists and agonists and prepulse inhibition which can then serve as a working model for an in-vivo efficacy of novel dopamine D2 drugs. The second part of the thesis work deals with Niemann pick disease type C. Niemann pick disease type C is a progressive genetic disorder that is characterized by the lysosomal accumulation of lipids which causes neurodegeneration, dementia, ataxia, and death. NPC1nmf164 mutant mice ...


Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji Jun 2021

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction (PCR) and ...


Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh Jun 2021

Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh

Pharmacy Faculty Articles and Research

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 ...


Efforts Toward Novel Methods For The Synthesis Of Stereochemically-Dense Pharmacologically Relevant Scaffolds, Lauren Nicole Tumbelty May 2021

Efforts Toward Novel Methods For The Synthesis Of Stereochemically-Dense Pharmacologically Relevant Scaffolds, Lauren Nicole Tumbelty

Theses and Dissertations

Nitrogen is the most common pure element, present in nearly all relevant chemical compounds. It is an essential component of the building blocks of life such as proteins, nucleic acids, amino acids and adenosine tri-phosphate. There is a naturally occurring exchange between living organisms and the atmosphere which begins with the process of fixation. Although nitrogen is naturally abundant, the strength of the triple bond in atmospheric nitrogen prevents its applicability in organic synthesis. Therefore, the development of methods to place synthetic nitrogen into heteroatomic compounds plays an important role in the development of pharmacologically relevant scaffolds. Contained within this ...


Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur May 2021

Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with a poor prognosis. While chemotherapeutics are potent, these agents lack specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment could lead to more safe and efficacious drugs. We previously engineered a breast cancer cell targeting peptide 18-4 that specifically binds cell surface receptor keratin 1 (K1) on breast cancer cells. A conjugate of peptide 18-4 and doxorubicin (Dox) containing an acid-sensitive hydrazone linker showed specific toxicity toward TNBC cells. Here, we report the ...


Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz May 2021

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca2+ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca2+ transients, but did not affect Ca2+ transients induced by high ...


Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner May 2021

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate ...


Comparison Of Canine And Human Physiological Factors: Understanding Interspecies Differences That Impact Drug Pharmacokinetics, Marilyn N. Martinez, Jonathan P. Mochel, Sibylle Neuhoff, Devendra Pade Apr 2021

Comparison Of Canine And Human Physiological Factors: Understanding Interspecies Differences That Impact Drug Pharmacokinetics, Marilyn N. Martinez, Jonathan P. Mochel, Sibylle Neuhoff, Devendra Pade

Biomedical Sciences Publications

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug ...


Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli Apr 2021

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative ...


Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ Apr 2021

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells ...


A Novel Molecular And Cellular Study On Curcumin, Khang Nguyen Apr 2021

A Novel Molecular And Cellular Study On Curcumin, Khang Nguyen

Undergraduate Research Conference

Since the discovery of G-quartet (G4)by M. Gellertin 1962, much attention has been given on G4and C4(also called i-motif) as important drug design targets for the treatment of various human disorders. G4 forming sequences are prevalent in human genome, which includes many important regions of the eukaryotic genome, such as telomere ends, regulatory regions of many oncogenes c-kit, proto-oncogene c-myc, Kirsten rat sarcoma viral oncogene homolog (KRas). Curcumin(diferuloylmethane), an antiinflammatory and antioxidant compound, is found in the rhizomes of the plant Curcuma longa. The phytopolyphenolic chemical curcumin has been in the prominence due to its diverse pharmacological ...


Study Of Potential Drug For Alzheimer’S Disease: Small Organic Molecules, 1,5-Dhn And Tmpyp Inhibit Amyloid-Β Peptide Aggregation And Quench Hydroxyl Radicals, Matthew Murphy Apr 2021

Study Of Potential Drug For Alzheimer’S Disease: Small Organic Molecules, 1,5-Dhn And Tmpyp Inhibit Amyloid-Β Peptide Aggregation And Quench Hydroxyl Radicals, Matthew Murphy

Undergraduate Research Conference

Alzheimer disease (AD) is recognized as the six leading cause of the death in the United States. As of now, there is no cure for this fatal disease. The current treatment methods can only temporarily slow the worsening of symptoms. Research data suggested that an excess generation of hydroxyl radical in the brain causing the aggregation of Amyloid-β (Aβ) peptide which is considered to be responsible for Alzheimer's disease. Thus, there is a pressing need to find a suitable drug which can quench hydroxyl radicals effectively and stop or slow down the formation of aggregation of Aβ peptide. The ...


C38: Exploring Doxorubicin-Mediated Hypertrophy And Cell Death In Primary Human Cardiomyocytes, Sonia Phan Apr 2021

C38: Exploring Doxorubicin-Mediated Hypertrophy And Cell Death In Primary Human Cardiomyocytes, Sonia Phan

Annual Research Symposium

No abstract provided.


Development Of Miriplatin-Loaded Nanoparticles Against Non-Small Cell Lung Cancer, Zhongyue Yuan, Zizhao Xu, Xin Guo Apr 2021

Development Of Miriplatin-Loaded Nanoparticles Against Non-Small Cell Lung Cancer, Zhongyue Yuan, Zizhao Xu, Xin Guo

Graduate and Professional Student Research Showcase

Lung cancer claims the highest mortality and the second-most new cases among all oncological diseases. NSCLC accounts for approximately 85% of all newly diagnosed lung cancers. Although platinum-based drugs are standard first-line chemotherapy for stage IIIB/IV NSCLC, accumulating reports have shown the failure of conventional platinum-based regimens due to drug resistance. Miriplatin is a lipophilic anti-cancer drug that has been approved in Japan for transcatheter arterial chemoembolization treatment of hepatocellular carcinoma. Lipid-based nanoparticles such as liposomes, micelles, and solid lipid nanoparticles (SLNs) can encapsulate anti-cancer drugs to improve their water solubility and bioavailability.


Pharmacological Blockade Of The 20-Hete Receptor Lowers Blood Pressure And Alters Vascular Function In Mice With Vascular Smooth Muscle- Specific Overexpression Of Cyp4a12-20-Hete Synthase, Kevin Agostinucci Mar 2021

Pharmacological Blockade Of The 20-Hete Receptor Lowers Blood Pressure And Alters Vascular Function In Mice With Vascular Smooth Muscle- Specific Overexpression Of Cyp4a12-20-Hete Synthase, Kevin Agostinucci

NYMC Student Theses and Dissertations

20-hydroxyeicosatetraenoic acid (20-HETE) is the ω-hydroxylation product of arachidonic acid catalyzed by CYP4A and 4F enzymes. 20-HETE is a vasoactive eicosanoid of the microcirculation exhibiting effects on both vascular smooth muscle cells (VSMC) and endothelial cells (EC). In VSMCs, 20-HETE’s bioactions include the stimulation of contraction, migration, and growth. In ECs, elevated 20-HETE is associated with reduced nitric oxide (NO) bioavailability, increased angiotensin converting enzyme (ACE) expression, and the promotion of inflammation. Recently in our laboratory, we identified GPR75 as a novel target of 20-HETE that promotes changes in blood pressure and vascular function. The aim of this study ...


Categorization Of Marketed Artificial Tear Formulations Based On Their Ingredients: A Rational Approach For Their Use, Avani Kathuria, Kiumars Shamloo, Vishal Jhanji, Ajay Sharma Mar 2021

Categorization Of Marketed Artificial Tear Formulations Based On Their Ingredients: A Rational Approach For Their Use, Avani Kathuria, Kiumars Shamloo, Vishal Jhanji, Ajay Sharma

Pharmacy Faculty Articles and Research

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and ...


Anti‑Estrogenic And Anti‑Aromatase Activities Of Citrus Peels Major Compounds In Breast Cancer, Maha Salama, Dina Mahmoud Elkersh, Shahira M. Ezzat, Yasmeen Attiaa, Engy A. Mahrous, Mohey Elmazar Mar 2021

Anti‑Estrogenic And Anti‑Aromatase Activities Of Citrus Peels Major Compounds In Breast Cancer, Maha Salama, Dina Mahmoud Elkersh, Shahira M. Ezzat, Yasmeen Attiaa, Engy A. Mahrous, Mohey Elmazar

Pharmacy

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling ...


N-Nitrosodimethylamine (Ndma) Contamination Of Ranitidine Products: A Review Of Recent Findings, Fahad S. Aldawsari, Yahya M. Alshehri, Thamer S. Alghamdi Mar 2021

N-Nitrosodimethylamine (Ndma) Contamination Of Ranitidine Products: A Review Of Recent Findings, Fahad S. Aldawsari, Yahya M. Alshehri, Thamer S. Alghamdi

Journal of Food and Drug Analysis

Ranitidine is a medication that has been used to alleviate heartburn and other disorders for over 40 years. Following reports of N-nitrosodimethylamine (NDMA) contamination in ranitidine products, there have been many recalls and registration suspensions. Here, we revise the literature information confirming ranitidine association with NDMA. Then, we highlight the documented mechanisms for NDMA release from ranitidine. In addition, the stability issue for this medicine is discussed. After that, we review and discuss the results of the United States Food and Drug Administration and the Australian Therapeutic Goods Administration laboratory testing of ranitidine products and the detected NDMA levels. Finally ...


Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma Feb 2021

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance ...


Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan Feb 2021

Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan

Pharmacy Faculty Articles and Research

Background

The ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.

Results

To characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately ...


Repurposing Of Omarigliptin As A Neuroprotective Agent Based On Docking With A2a Adenosine And Ache Receptors, Brain Glp-1 Response And Its Brain/Plasma Concentration Ratio After 28 Days Multiple Doses In Rats Using Lc-Ms/Ms, Bassam Ayoub, Haidy Michel, Shereen Mowaka, Moataz S. Hendy, Mariam M. Tadros Feb 2021

Repurposing Of Omarigliptin As A Neuroprotective Agent Based On Docking With A2a Adenosine And Ache Receptors, Brain Glp-1 Response And Its Brain/Plasma Concentration Ratio After 28 Days Multiple Doses In Rats Using Lc-Ms/Ms, Bassam Ayoub, Haidy Michel, Shereen Mowaka, Moataz S. Hendy, Mariam M. Tadros

Pharmacy

Abstract: The authors in the current work suggested the potential repurposing of omarigliptin (OMR) for neurodegenerative diseases based on three new findings that support the preliminary finding of crossing BBB after a single dose study in the literature. The first finding is the positive results of the docking study with the crystal structures of A2A adenosine (A2AAR) and acetylcholine esterase (AChE) receptors. A2AAR is a member of non-dopaminergic GPCR superfamily receptor proteins and has essential role in regulation of glutamate and dopamine release in Parkinson’s disease while AChE plays a major role in Alzheimer’s disease as the primary ...


Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli Feb 2021

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the ...


The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba Jan 2021

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted ...


Nad(H) Phosphates Mediate Tetramer Assembly Of Human C-Terminal Binding Protein (Ctbp), Jeffry C. Nichols, Celia A. Schiffer, William E. Royer Jan 2021

Nad(H) Phosphates Mediate Tetramer Assembly Of Human C-Terminal Binding Protein (Ctbp), Jeffry C. Nichols, Celia A. Schiffer, William E. Royer

University of Massachusetts Medical School Faculty Publications

C-terminal binding proteins (CtBPs) are co-transcriptional factors that play key roles in cell fate. We have previously shown that NAD(H) promotes the assembly of similar tetramers from either human CtBP1 and CtBP2 and that CtBP2 tetramer destabilizing mutants are defective for oncogenic activity. To assist structure-based design efforts for compounds that disrupt CtBP tetramerization, it is essential to understand how NAD(H) triggers tetramer assembly. Here, we investigate the moieties within NAD(H) that are responsible for triggering tetramer formation. Using multi-angle light scattering (MALS) we show that ADP is able to promote tetramer formation of both CtBP1 and ...


Synergistic Interactions Of Ionic Liquids And Antimicrobials Improve Drug Efficacy., Daniel D Yang, Nicholas J Paterna, Alexandria S Senetra, Kaitlyn R Casey, Phillip D Trieu, Gregory A. Caputo, Timothy Vaden, Benjamin Carone Jan 2021

Synergistic Interactions Of Ionic Liquids And Antimicrobials Improve Drug Efficacy., Daniel D Yang, Nicholas J Paterna, Alexandria S Senetra, Kaitlyn R Casey, Phillip D Trieu, Gregory A. Caputo, Timothy Vaden, Benjamin Carone

Faculty Scholarship for the College of Science & Mathematics

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and ...


A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth Jan 2021

A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth

Pharmacy Faculty Articles and Research

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s ...


Site-Specific Incorporation Of Citrulline Into Proteins In Mammalian Cells, Santanu Mondal, Shu Wang, Yunan Zheng, Sudeshna Sen, Abhishek Chatterjee, Paul R. Thompson Jan 2021

Site-Specific Incorporation Of Citrulline Into Proteins In Mammalian Cells, Santanu Mondal, Shu Wang, Yunan Zheng, Sudeshna Sen, Abhishek Chatterjee, Paul R. Thompson

University of Massachusetts Medical School Faculty Publications

Citrullination is a post-translational modification (PTM) of arginine that is crucial for several physiological processes, including gene regulation and neutrophil extracellular trap formation. Despite recent advances, studies of protein citrullination remain challenging due to the difficulty of accessing proteins homogeneously citrullinated at a specific site. Herein, we report a technology that enables the site-specific incorporation of citrulline (Cit) into proteins in mammalian cells. This approach exploits an engineered E. coli-derived leucyl tRNA synthetase-tRNA pair that incorporates a photocaged-citrulline (SM60) into proteins in response to a nonsense codon. Subsequently, SM60 is readily converted to Cit with light in vitro and in ...


Pharmacogenomics And Ssris Appropriateness In Older Community Dwelling African Americans, Wint War Phyo, Lana Sargent, Elvin T. Price Jan 2021

Pharmacogenomics And Ssris Appropriateness In Older Community Dwelling African Americans, Wint War Phyo, Lana Sargent, Elvin T. Price

Graduate Research Posters

Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.

Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the ...


Peptidomimetic And Non- Peptidomimetic Derivatives As Possible Sars-Cov-2 Main Protease (Mpro) Inhibitors, Mohammed A. Al Awadh, Mohini S. Ghatge Ph.D, Mona A. Al Khairi, Faik N. Musayev, Akua K. Donkor, Mohammed H. Al Mughram, Abdelsattar M. Omar Ph.D, Moustafa M. El-Araby Ph.D, Martin K. Safo Ph.D Jan 2021

Peptidomimetic And Non- Peptidomimetic Derivatives As Possible Sars-Cov-2 Main Protease (Mpro) Inhibitors, Mohammed A. Al Awadh, Mohini S. Ghatge Ph.D, Mona A. Al Khairi, Faik N. Musayev, Akua K. Donkor, Mohammed H. Al Mughram, Abdelsattar M. Omar Ph.D, Moustafa M. El-Araby Ph.D, Martin K. Safo Ph.D

Graduate Research Posters

To design novel inhibitors of the SARS-CoV-2 main protease (Mpro), we investigated the binding mode of the recently reported α-ketoamide inhibitors of this enzyme. Following, we utilized in-silico screening to identify 168 peptidomimetic and non-peptidomimetic compounds that are high probability Mpro binding candidates. The compounds were synthesized in 5 to 10 mg for initial screening for their potential inhibition of Mpro using Fluorescence Resonance Energy Transfer (FRET) assay. The study was conducted using the main protease, MBP-tagged (SARS-CoV-2) Assay Kit (BPS Bioscience, #79955-2), and the fluorescence due to enzymatic cleavage of substrate measured using BMG LABTECH CLARIOstar™, a fluorescent microplate ...


Evaluation Of Antipsychotic Activity Of Ethanolic Bark Extract Of Myrica Esculenta In Rats, Biswash Sapkota, Ankit Acharya, Bishal Dangi, Annegowda Hv Dec 2020

Evaluation Of Antipsychotic Activity Of Ethanolic Bark Extract Of Myrica Esculenta In Rats, Biswash Sapkota, Ankit Acharya, Bishal Dangi, Annegowda Hv

Pharmaceutical Sciences and Research

The antipsychotic properties of Myrica esculenta stem bark were evaluated. The stem bark was collected, shade dried, and pulverized. Extraction was carried out with 70% ethanol by occasional shaking. Preliminary phytochemical screening of the extract was investigated in this study. Antipsychotic activity was evaluated against apomorphine-induced stereotypy using cook’s pole climbing apparatus and haloperidol-induced catalepsy models. Bioamine determination of noradrenaline and dopamine was also performed. The extract contains phytochemicals, including glycosides, flavonoids, volatile oils, proteins, saponins, phenolics, and tannins. The result showed decreased apomorphine-induced stereotyped behavior. This study reported significant dose-dependent potentiation of haloperidol-induced catalepsy in rats and a ...