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Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma Jun 2023

Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma

Chemistry and Biochemistry Publications

Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To address this limitation, we present a comprehensive analysis of base stacks involving all crystallographic occurrences of the most biologically relevant modified bases in a large dataset of high-resolution RNA crystal structures. This is accompanied by a geometrical classification of the stacking contacts using our established tools. Coupled with quantum chemical calculations and an analysis …


Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma Jun 2023

Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma

Chemistry and Biochemistry Publications

Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To address this limitation, we present a comprehensive analysis of base stacks involving all crystallographic occurrences of the most biologically relevant modified bases in a large dataset of high-resolution RNA crystal structures. This is accompanied by a geometrical classification of the stacking contacts using our established tools. Coupled with quantum chemical calculations and an analysis …


Mitocans Induce Lipid Flip-Flop And Permeabilize The Membrane To Signal Apoptosis, Stuart R. Castillo, Michael H.L. Nguyen, Mitchell Dipasquale, Elizabeth G. Kelley, Drew Marquardt Jun 2023

Mitocans Induce Lipid Flip-Flop And Permeabilize The Membrane To Signal Apoptosis, Stuart R. Castillo, Michael H.L. Nguyen, Mitchell Dipasquale, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and x-ray scattering in combination with calcein leakage assays to characterize the effects of PST, NRC, and tamoxifen (TAM) on a biomimetic model membrane. We report an increase in lipid …


Boron Neutron Capture Therapy In The New Age Of Accelerator-Based Neutron Production And Preliminary Progress In Canada, Dominik Dziura, Sana Tabbassum, Amanda Macneil, Dalini D. Maharaj, Robert Laxdal, Oliver Kester, Ming Pan, Hiroaki Kumada, Drew Marquardt Jun 2023

Boron Neutron Capture Therapy In The New Age Of Accelerator-Based Neutron Production And Preliminary Progress In Canada, Dominik Dziura, Sana Tabbassum, Amanda Macneil, Dalini D. Maharaj, Robert Laxdal, Oliver Kester, Ming Pan, Hiroaki Kumada, Drew Marquardt

Chemistry and Biochemistry Publications

Each year more than 3000 Canadians are diagnosed with brain cancers like glioblastoma multiforme or recurrent head and neck cancers, which are difficult to treat with conventional radiotherapy techniques. One of the most clinically promising treatments for these cancers is boron neutron capture therapy (BNCT). This procedure involves selectively introducing a boron delivery agent into tumor cells and irradiating them with a neutron beam, which kills the cancer cells due to the high-linear energy transfer radiation produced by the 10B(n,α)7Li capture reaction. The theory of BNCT has been around for a long time since 1936, but has historically been limited …


Investigating The Effect Of Medium Chain Triglycerides On The Elasticity Of Pulmonary Surfactant, Maksymilian Dziura, Stuart R. Castillo, Mitchell Dipasquale, Omotayo Gbadamosi, Piotr Zolnierczuk, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt Apr 2023

Investigating The Effect Of Medium Chain Triglycerides On The Elasticity Of Pulmonary Surfactant, Maksymilian Dziura, Stuart R. Castillo, Mitchell Dipasquale, Omotayo Gbadamosi, Piotr Zolnierczuk, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

In recent years, vaping has increased in both popularity and ease of access. This has led to an outbreak of a relatively new condition known as e-cigarette/vaping-associated lung injury (EVALI). This injury can be caused by physical interactions between the pulmonary surfactant (PS) in the lungs and toxins typically found in vaping solutions, such as medium chain triglycerides (MCT). MCT has been largely used as a carrier agent within many cannabis products commercially available on the market. Pulmonary surfactant ensures proper respiration by maintaining low surface tensions and interface stability throughout each respiratory cycle. Therefore, any impediments to this system …


“Breaking Bud”: The Effect Of Direct Chemical Modifications Of Phytocannabinoids On Their Bioavailability, Physiological Effects, And Therapeutic Potential, Abhinandan Banerjee, John J. Hayward, John F. Trant Feb 2023

“Breaking Bud”: The Effect Of Direct Chemical Modifications Of Phytocannabinoids On Their Bioavailability, Physiological Effects, And Therapeutic Potential, Abhinandan Banerjee, John J. Hayward, John F. Trant

Chemistry and Biochemistry Publications

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two “major cannabinoids”. However, their incorporation into clinical and nutraceutical preparations is challenging, owing to their limited bioavailability, low water solubility, and variable pharmacokinetic profiles. Understanding the organic chemistry of the major cannabinoids provides us with potential avenues to overcome these issues through derivatization. The resulting labile pro-drugs offer ready cannabinoid release in vivo, have augmented bioavailability, or demonstrate interesting pharmacological properties in their own right. This review identifies and discusses a subset of these advanced derivatization strategies for the major cannabinoids, where the starting material is the pure phytocannabinoid itself, and …


The “Nitrogen Effect”: Complexation With Macrocycles Potentiates Fused Heterocycles To Form Halogen Bonds In Competitive Solvents, Dr. Kwaku Twum, Sanaz Nadimi, Frank Boateng Osei, Dr. Rakesh Puttreddy, Dr. Yvonne Bessem Ojong, Dr. John J. Hayward, Prof. Kari Rissanen, Prof. John F. Trant, Prof. Ngong Kodiah Beyeh Kodiah Beyeh Jan 2023

The “Nitrogen Effect”: Complexation With Macrocycles Potentiates Fused Heterocycles To Form Halogen Bonds In Competitive Solvents, Dr. Kwaku Twum, Sanaz Nadimi, Frank Boateng Osei, Dr. Rakesh Puttreddy, Dr. Yvonne Bessem Ojong, Dr. John J. Hayward, Prof. Kari Rissanen, Prof. John F. Trant, Prof. Ngong Kodiah Beyeh Kodiah Beyeh

Chemistry and Biochemistry Publications

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three-component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N-heterocycles in an open resorcinarene cavity to template the formation of a three-component halogen-bonded ternary assembly in a protic polar solvent system.


Structural And Energetic Features Of Base–Base Stacking Contacts In Rna, Zakir Ali, Ambika Goyal, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma Jan 2023

Structural And Energetic Features Of Base–Base Stacking Contacts In Rna, Zakir Ali, Ambika Goyal, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma

Chemistry and Biochemistry Publications

Nucleobase π–π stacking is one of the crucial organizing interactions within three-dimensional (3D) RNA architectures. Characterizing the structural variability of these contacts in RNA crystal structures will help delineate their subtleties and their role in determining function. This analysis of different stacking geometries found in RNA X-ray crystal structures is the largest such survey to date; coupled with quantum-mechanical calculations on typical representatives of each possible stacking arrangement, we determined the distribution of stacking interaction energies. A total of 1,735,481 stacking contacts, spanning 359 of the 384 theoretically possible distinct stacking geometries, were identified. Our analysis reveals preferential occurrences of …


Investigating The Cut-Off Effect Of N-Alcohols On Lipid Movement: A Biophysical Study, Michael H.K. Nguyen, Dominik Dziura, Mitchell Dipasquale, Stuart R. Castillo, Elizabeth G. Kelley, Drew Marquardt Jan 2023

Investigating The Cut-Off Effect Of N-Alcohols On Lipid Movement: A Biophysical Study, Michael H.K. Nguyen, Dominik Dziura, Mitchell Dipasquale, Stuart R. Castillo, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

Cellular membranes are responsible for absorbing the effects of external perturbants for the cell’s survival. Such perturbants include small ubiquitous molecules like n-alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of nalcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TRSANS), small angle X-ray …


Biallelic Mutations In P4htm Cause Syndromic Obesity, Sadia Saeed, Lijiao Ning, Alaa Badreddine, Muhammad Usman Mirza, Mathilde Boissel, Roohia Khanam, Jaida Manzoor, Qasim M. Janjua, Waqas I. Khan, Bénédicte Toussaint, Emmanuel Vaillant, Souhila Amanzougarene, Mehdi Derhourhi, John F. Trant, Anna-Maria Siegert, Brian Y.H. Lam, Giles S.H. Yeo, Layachi Chabraoui, Asmae Touzani, Abhishek Kulkarni, I. Sadaf Farooqi, Amélie Bonnefond, Muhammad Arslan, Philippe Froguel Jan 2023

Biallelic Mutations In P4htm Cause Syndromic Obesity, Sadia Saeed, Lijiao Ning, Alaa Badreddine, Muhammad Usman Mirza, Mathilde Boissel, Roohia Khanam, Jaida Manzoor, Qasim M. Janjua, Waqas I. Khan, Bénédicte Toussaint, Emmanuel Vaillant, Souhila Amanzougarene, Mehdi Derhourhi, John F. Trant, Anna-Maria Siegert, Brian Y.H. Lam, Giles S.H. Yeo, Layachi Chabraoui, Asmae Touzani, Abhishek Kulkarni, I. Sadaf Farooqi, Amélie Bonnefond, Muhammad Arslan, Philippe Froguel

Chemistry and Biochemistry Publications

We previously demonstrated that 50% of children with obesity from consanguineous families from Pakistan carry pathogenic variants in known monogenic obesity genes. Here, we have discovered a novel monogenetic recessive form of severe childhood obesity using an in-house computational staged approach. The analysis included whole-exome sequencing data of 366 children with severe obesity, 1,000 individuals of the Pakistan Risk of Myocardial Infarction Study (PROMIS) study, and 200,000 participants of the UK Biobank to prioritize genes harboring rare homozygous variants with putative effect on human obesity. We identified five rare or novel homozygous missense mutations predicted deleterious in five consanguineous families …


Guanidinium–Amino Acid Hydrogen-Bonding Interactions In Protein Crystal Structures: Implications For Guanidinium-Induced Protein Denaturation, Indu Negi, Raman Jangra, Amit Gharu, John F. Trant, Purshotam Sharma Dec 2022

Guanidinium–Amino Acid Hydrogen-Bonding Interactions In Protein Crystal Structures: Implications For Guanidinium-Induced Protein Denaturation, Indu Negi, Raman Jangra, Amit Gharu, John F. Trant, Purshotam Sharma

Chemistry and Biochemistry Publications

In the present work, 86 available high resolution X-ray structures of proteins that contain one or more guanidinium ions (Gdm+) are analyzed for the distribution and nature of noncovalent interactions between Gdm+ and amino-acid residues. A total of 1044 hydrogen-bonding interactions were identified, of which 1039 are N–H⋯O, and five are N–H⋯N. Acidic amino acids are more likely to interact with Gdm+ (46% of interactions, 26% Asp and 20% Glu), followed by Pro (19% of interactions). DFT calculations on the identified Gdm+–amino acid hydrogen-bonded pairs reveal that although Gdm+ interacts primarily with the backbone amides of nonpolar amino acids, Gdm+ …


A Nanodiamond Chemotherapeutic Folate Receptor-Targeting Prodrug With Triggerable Drug Release, Jiangtao Wu, Xiangbin Du, Dongmei Zhang, Jicheng Cui, Xiaoxia Zhang, Xine Duan, John F. Trant, Yingqi Li Nov 2022

A Nanodiamond Chemotherapeutic Folate Receptor-Targeting Prodrug With Triggerable Drug Release, Jiangtao Wu, Xiangbin Du, Dongmei Zhang, Jicheng Cui, Xiaoxia Zhang, Xine Duan, John F. Trant, Yingqi Li

Chemistry and Biochemistry Publications

No abstract provided.


Vitamin E Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains, Mitchell Dipasquale, Michael H.L. Nguyen, Stuart R. Castillo, Isabelle J. Dib, Elizabeth G. Kelley, Drew Marquardt Nov 2022

Vitamin E Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains, Mitchell Dipasquale, Michael H.L. Nguyen, Stuart R. Castillo, Isabelle J. Dib, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in …


Partial Volumes Of Phosphatidylcholines And Vitamin E: Α-Tocopherol Prefers Disordered Membranes, Mitchell Dipasquale, Michael H.L. Nguyen, Georg Pabst, Drew Marquardt Sep 2022

Partial Volumes Of Phosphatidylcholines And Vitamin E: Α-Tocopherol Prefers Disordered Membranes, Mitchell Dipasquale, Michael H.L. Nguyen, Georg Pabst, Drew Marquardt

Chemistry and Biochemistry Publications

Despite its discovery over 95 years ago, the biological and nutritional roles of vitamin E remain subjects of much controversy. Though it is known to possess antioxidant properties, recent assertions have implied that vitamin E may not be limited to this function in living systems. Through densitometry measurements and small-angle X-ray scattering we observe favorable interactions between α-tocopherol and unsaturated phospholipids, with more favorable interactions correlating to an increase in lipid chain unsaturation. Our data provide evidence that vitamin E may preferentially associate with oxygen sensitive lipids-an association that is considered innate for a viable membrane antioxidant.


Novel Quinoline-Derived Chemosensors: Synthesis, Anion Recognition, Spectroscopic, And Computational Study†, Tahira Saleem, Samra Khan, Muhammad Yaqub, Muhammad Khalid, Muhammad Islam, Muhammad Yousaf Ur Rehman, Muhammad Rashid, Iqra Shafiq, Ataualpa A. C. Braga, Asad Syed, Ali H. Bahkali, John F. Trant, Zahid Shafiq Aug 2022

Novel Quinoline-Derived Chemosensors: Synthesis, Anion Recognition, Spectroscopic, And Computational Study†, Tahira Saleem, Samra Khan, Muhammad Yaqub, Muhammad Khalid, Muhammad Islam, Muhammad Yousaf Ur Rehman, Muhammad Rashid, Iqra Shafiq, Ataualpa A. C. Braga, Asad Syed, Ali H. Bahkali, John F. Trant, Zahid Shafiq

Chemistry and Biochemistry Publications

Fluorescent-small molecules offer an excellent source of chemosensors when optimized for detection of anions with sensitivity and selectivity, low-cost and robust synthesis. In the present study we synthesized new quinoline-based chemosensors (4a–e) via the one-pot multi component reaction and confirmed their potential for chemosensory via cyclic voltammetry. 4a–e were tested for ligand–anion interaction against F−, OAc−, Br−, ClO3, I−, HSO4−, CN−, ClO4− and SCN-ions, by using UV-visible, colorimetry and Fluorescence. The NH deprotonation was observed as the mechanism of anion interaction via FTIR and H1NMR spectroscopies. Benesi–Hildebrand plot was drawn to calculate binding constants and limit of detection was also …


A Revised Synthesis Of 6-Alkoxy-2-Aminopurines With Late-Stage Convergence Allowing For Increased Molecular Complexity†, Lavleen Mader, John J. Hayward, Lisa A. Porter, John F. Trant Aug 2022

A Revised Synthesis Of 6-Alkoxy-2-Aminopurines With Late-Stage Convergence Allowing For Increased Molecular Complexity†, Lavleen Mader, John J. Hayward, Lisa A. Porter, John F. Trant

Chemistry and Biochemistry Publications

6-Alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E complexes has previously involved a thorough investigation of structure activity relationships of the C-2 amine moiety. However, the established synthesis of these compounds, which uses the alcohol reagent as solvent, limits the complexity of the O-6 functionality which is required for more selective targeting. Herein we report an improved and refocused synthesis of a model CDK2 inhibitor (NU6247), affording convenient access to inhibitors with O-6 substituents whose parent alcohol is …


The Interaction Of Deep Eutectic Solvents With Pristine Carbon Nanotubes And Their Associated Defects: A Density Functional Theory Study, Hamid Reza Ghenaatian, Mehdi Shakourian-Fard, Ganesh Kamath, John F. Trant, Farouq S. Mjalli Jul 2022

The Interaction Of Deep Eutectic Solvents With Pristine Carbon Nanotubes And Their Associated Defects: A Density Functional Theory Study, Hamid Reza Ghenaatian, Mehdi Shakourian-Fard, Ganesh Kamath, John F. Trant, Farouq S. Mjalli

Chemistry and Biochemistry Publications

In this study, the interaction of four deep eutectic solvents (DESs): [Choline chloride][Urea] ([ChCl][U]), [Choline chloride][Ethylene glycol] ([ChCl][EG]), [Choline chloride][Glycerol] ([ChCl][Gly]) and [Choline chloride][Benzoic acid] ([ChCl][BA]), with pristine carbon nanotube (CNT) and its defects: double-vacancy and Stone–Wales structures (CNT-DV and CNT-SW) is investigated using density functional theory (DFT) calculations. The geometry optimization, electronic property calculations, noncovalent interaction analysis and optical properties of the DES@nanotube complexes were carried out at the M06-2X/cc-pVDZ level of theory. The adsorption energy (Eads) calculations show that the presence of the DV and SW defects on the CNT increases the adsorption strength of the DESs, DES@CNT-SW …


The Total Synthesis Of Glycolipids From Streptococcus Pneumoniae And A Re-Evaluation Of Their Immunological Activity**, Seyed Iraj Sadraei, Greg Yousif, S. Maryamdokht Taimoory, Maryam Kosar, Samaneh Mehri, Raghd Alolabi, Emmanuel Igbokwe, Jason Toma, Mir Munir A. Rahim, John F. Trant Jul 2022

The Total Synthesis Of Glycolipids From Streptococcus Pneumoniae And A Re-Evaluation Of Their Immunological Activity**, Seyed Iraj Sadraei, Greg Yousif, S. Maryamdokht Taimoory, Maryam Kosar, Samaneh Mehri, Raghd Alolabi, Emmanuel Igbokwe, Jason Toma, Mir Munir A. Rahim, John F. Trant

Chemistry and Biochemistry Publications

Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi-invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility complex, conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor's first potent identified antigen is the α-galactosylceramide, KRN7000, a synthetic glycosphingolipid closely related to those isolated from bacteria that were found on a Japanese marine sponge. A corresponding terrestrial antigen remained …


The Interaction And Orientation Of Peptide Kl4 In Model Membranes, Drew Marquardt, Brad Van Oosten, Maksymilian Dziura, Joanna R. Long, Thad A. Harroun Jul 2022

The Interaction And Orientation Of Peptide Kl4 In Model Membranes, Drew Marquardt, Brad Van Oosten, Maksymilian Dziura, Joanna R. Long, Thad A. Harroun

Chemistry and Biochemistry Publications

We report on the orientation and location of synthetic pulmonary surfactant peptide KL4, (KLLLL)4K, in model lipid membranes. The partitioning depths of selectively deuterated leucine residues within KL4 were determined in DPPC:POPG (4:1) and POPC:POPG (4:1) bilayers by oriented neutron diffraction. These measurements were combined with an NMR-generated model of the peptide structure to determine the orientation and partitioning of the peptide at the lipid–water interface. The results demonstrate KL4 adopting an orientation that interacts with a single membrane leaflet. These observations are consistent with past 2H NMR and EPR studies (Antharam et al., 2009; Turner et al., 2014).


Guest-Mediated Self-Assembly Of Deprotonated 2-Bromoresorcinarenes, Kwaku Twum, Khai-Nghi Truong, Frank Boateng Osei, Carolina Von Essen, Sanaz Nadimi, John F. Trant, Kari Rissanen, Ngong Kodiah Beyeh Jul 2022

Guest-Mediated Self-Assembly Of Deprotonated 2-Bromoresorcinarenes, Kwaku Twum, Khai-Nghi Truong, Frank Boateng Osei, Carolina Von Essen, Sanaz Nadimi, John F. Trant, Kari Rissanen, Ngong Kodiah Beyeh

Chemistry and Biochemistry Publications

Doubly and triply deprotonated 2-bromo-C-alkylresorcinarene anions form host–guest complexes with both tetramethylammonium cations and bis-protonated dimethyl piperazine cations. The trianion forms a fully closed dimeric capsule with one endo- and two exo-cavity bis-protonated dimethyl piperazine cations. Interestingly, the dianion crystallized from a mixture of the 2-bromo-C-methylresorcinarene, dimethylethylenediamine, and tetramethylammonium chloride forms a nanotube consisting of only the 2-bromo-C-methylresorcinarene anion and the tetramethylammonioum cation. The nanotube has an exo-functionalized anionic hydrophilic outer surface that interacts with cationic guests and a hydrophobic interior channel. Solution studies support the deprotonation and the formation of these …


Probing The Link Between Pancratistatin And Mitochondrial Apoptosis Through Changes In The Membrane Dynamics On The Nanoscale, Stuart R. Castillo, Brett W. Rickeard, Mitchell Dipasquale, Michael H.L. Nguyen, Aislyn Lewis-Laurent, Milka Doktorova, Batuhan Kav, Markus S. Miettinen, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt Jun 2022

Probing The Link Between Pancratistatin And Mitochondrial Apoptosis Through Changes In The Membrane Dynamics On The Nanoscale, Stuart R. Castillo, Brett W. Rickeard, Mitchell Dipasquale, Michael H.L. Nguyen, Aislyn Lewis-Laurent, Milka Doktorova, Batuhan Kav, Markus S. Miettinen, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

Pancratistatin (PST) is a natural antiviral alkaloid that has demonstrated specificity toward cancerous cells and explicitly targets the mitochondria. PST initiates apoptosis while leaving healthy, noncancerous cells unscathed. However, the manner by which PST induces apoptosis remains elusive and impedes the advancement of PST as a natural anticancer therapeutic agent. Herein, we use neutron spin-echo (NSE) spectroscopy, molecular dynamics (MD) simulations, and supporting small angle scattering techniques to study PST's effect on membrane dynamics using biologically representative model membranes. Our data suggests that PST stiffens the inner mitochondrial membrane (IMM) by being preferentially associated with cardiolipin, which would lead to …


Naphthalene-Functionalized Resorcinarene As Selective, Fluorescent Self-Quenching Sensor For Kynurenic Acid†, Anna Karle, Kwaku Twum, Noorhan Sabbagh, Alise Haddad, S. Maryamdokht Taimoory, Małgorzata M. Szczęśniak, Evan Trivedi, John F. Trant, Ngong Kodiah Beyeh Apr 2022

Naphthalene-Functionalized Resorcinarene As Selective, Fluorescent Self-Quenching Sensor For Kynurenic Acid†, Anna Karle, Kwaku Twum, Noorhan Sabbagh, Alise Haddad, S. Maryamdokht Taimoory, Małgorzata M. Szczęśniak, Evan Trivedi, John F. Trant, Ngong Kodiah Beyeh

Chemistry and Biochemistry Publications

Kynurenic acid is a by-product of tryptophan metabolism in humans, with abnormal levels indicative of disease. There is a need for water-soluble receptors that selectively bind kynurenic acid, allowing for detection and quantification. We report here the high-affinity binding of kynurenic acid in aqueous media to a resorcinarene salt receptor decorated with four flexible naphthalene groups at the upper rim. Experimental results from 1H NMR, isothermal titration calorimetry, and electronic absorption and fluorescence spectroscopies all support high-affinity binding and selectivity for kynurenic acid over tryptophan. The measured binding constant (K = 1.46 ± 0.21 × 105 M−1) is one …


Effect Of Mono-Vacant Defects On The Adsorption Properties Of Deep Eutectic Solvents Onto Hexagonal Boron-Nitride Nanoflakes, Mehdi Shakourian-Fard, S. Maryamdokht Taimoory, Hamid Reza Ghenaatian, Ganesh Kamath, John F. Trant Mar 2022

Effect Of Mono-Vacant Defects On The Adsorption Properties Of Deep Eutectic Solvents Onto Hexagonal Boron-Nitride Nanoflakes, Mehdi Shakourian-Fard, S. Maryamdokht Taimoory, Hamid Reza Ghenaatian, Ganesh Kamath, John F. Trant

Chemistry and Biochemistry Publications

Hexagonal boron nitride is a promising material for a variety of electronic, optical, and material science applications. Both the synthesis of the material through exfoliation, and its various applications almost inevitably require its solvation. Deep eutectic solvents (DES) are extremely useful solvents for these types of applications due to their non-volatility, inflammability, biocompatibility, and reasonable cost. There are many different deep eutectic solvents available, and their suitability for any given application is particularly dependent on the specific of their structure. DES have been examined computationally for use with boron nitride, but these calculations use idealized, perfect boron nitride sheets instead …


Flexible And Printed Electronics: A Transition In Leadership - Reflecting On Our Successes And Looking Forward To The Future, Tricia Breen Carmichael, Ronald Österbacka Mar 2022

Flexible And Printed Electronics: A Transition In Leadership - Reflecting On Our Successes And Looking Forward To The Future, Tricia Breen Carmichael, Ronald Österbacka

Chemistry and Biochemistry Publications

No abstract provided.


Giving Preparative Thin-Layer Chromatography Some Tender ­Loving Care, John J. Hayward, Lavleen Mader, John F. Trant Feb 2022

Giving Preparative Thin-Layer Chromatography Some Tender ­Loving Care, John J. Hayward, Lavleen Mader, John F. Trant

Chemistry and Biochemistry Publications

Preparative thin-layer chromatography (prepTLC) is a commonly used method of purification suitable for small-scale reactions. However, descriptions of the preferred methodology to load, run, and recover samples from prepTLC are non-standard and varied, making it part of the ‘hidden curriculum’ of laboratory techniques. In this article we report on the simple, cost-effective methods we use to load and collect samples from a plate, which enhance the convenience, speed, and precision of this technique.


Fabrication And Characterization Of Autonomously Self-Healable And Stretchable Soft Microfluidics, Hualong Wang, Susanna Vu, Julia Pignanelli, Tamer Abdel Fatah, John F. Trant, Sara Mahshid, Simon Rondeau-Gagné, Mohammed Jalal Ahamed Feb 2022

Fabrication And Characterization Of Autonomously Self-Healable And Stretchable Soft Microfluidics, Hualong Wang, Susanna Vu, Julia Pignanelli, Tamer Abdel Fatah, John F. Trant, Sara Mahshid, Simon Rondeau-Gagné, Mohammed Jalal Ahamed

Chemistry and Biochemistry Publications

In this paper, a novel self-healable and stretchable microfluidics system for next generation wearable lab-on-a-chip is presented. An imine-based precursor with various metal sources (Co(II), Fe(II), and Zn(II)) is used for the development of an intrinsically autonomous self-healing microfluidic device. Microfluidics fabrication is performed on the self-healing substrate layer using a mold transfer method. The mechanical properties of the resulting layer are evaluated using tensile strain pull testing. Microfluidic characteristics including fluid flow, wettability, leak, and fluorescence compatibility are investigated to understand its performance in classical microfluidic applications. The new microfluidic devices are also characterized using scanning-electron microscopy to evaluate …


Identification Of Alternative Protein Targets Of Glutamate-Ureido-Lysine Associated With Psma Tracer Uptake In Prostate Cancer Cells, Martin K. Bakht, John J. Hayward, Farsheed Shahbazi-Raz, Magdalena Skubal, Ryo Tamura, Keith F. Stringer, Daniel Meister, Varadha Balaji Venkadakrishnan, Hui Xue, Adam Pillon, Mathew Stover, Adam Tronchin, Bre Anne Fifield, Lavleen Mader, Sheng Yu Ku, Gi Jeong Cheon, Keon Wook Kang, Yuzhuo Wang, Xuesen Dong, Himisha Beltran, Jan Grimm, Lis A. Porter, John F. Trant Jan 2022

Identification Of Alternative Protein Targets Of Glutamate-Ureido-Lysine Associated With Psma Tracer Uptake In Prostate Cancer Cells, Martin K. Bakht, John J. Hayward, Farsheed Shahbazi-Raz, Magdalena Skubal, Ryo Tamura, Keith F. Stringer, Daniel Meister, Varadha Balaji Venkadakrishnan, Hui Xue, Adam Pillon, Mathew Stover, Adam Tronchin, Bre Anne Fifield, Lavleen Mader, Sheng Yu Ku, Gi Jeong Cheon, Keon Wook Kang, Yuzhuo Wang, Xuesen Dong, Himisha Beltran, Jan Grimm, Lis A. Porter, John F. Trant

Chemistry and Biochemistry Publications

Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMA-specific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based …


Identifying Membrane Lateral Organization By Contrast-Matched Small Angle Neutron Scattering, Mitchell Dipasquale, Michael H.L. Nguyen, Stuart R. Castillo, Frederick A. Heberle, Drew Marquardt Jan 2022

Identifying Membrane Lateral Organization By Contrast-Matched Small Angle Neutron Scattering, Mitchell Dipasquale, Michael H.L. Nguyen, Stuart R. Castillo, Frederick A. Heberle, Drew Marquardt

Chemistry and Biochemistry Publications

Lipid domains in model membranes are routinely studied to provide insight into the physical interactions that drive raft formation in cellular membranes. Using small angle neutron scattering, contrast-matching techniques enable the detection of lipid domains ranging from tens to hundreds of nanometers which are not accessible to other techniques without the use of extrinsic probes. Here, we describe a probe-free experimental approach and model-free analysis to identify lipid domains in freely floating vesicles of ternary phase separating lipid mixtures.


Influence Of Ceramide On Lipid Domain Stability Studied With Small-Angle Neutron Scattering: The Role Of Acyl Chain Length And Unsaturation, Mitchell Dipasquale, Tye G. Deering, Dhimant Desai, Arun K. Sharma, Shantu Amin, Todd E. Fox, Mark Kester, John Katsaras, Drew Marquardt, Frederick A. Heberle Jan 2022

Influence Of Ceramide On Lipid Domain Stability Studied With Small-Angle Neutron Scattering: The Role Of Acyl Chain Length And Unsaturation, Mitchell Dipasquale, Tye G. Deering, Dhimant Desai, Arun K. Sharma, Shantu Amin, Todd E. Fox, Mark Kester, John Katsaras, Drew Marquardt, Frederick A. Heberle

Chemistry and Biochemistry Publications

Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain- forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen's stable isotopes protium and deuterium. Specifcally, neutron contrast is generated …


Sharing The Salt Bowl: Counterion Identity Drives N-Alkyl Resorcinarene Affinity For Pyrophosphate In Water, Kwaku Twum, Seyed Iraj Sadraei, Jordan Feder, S. Maryamdokht Taimoory, Kari Rissanen, John F. Trant, Ngong Kodiah Beyeh Dec 2021

Sharing The Salt Bowl: Counterion Identity Drives N-Alkyl Resorcinarene Affinity For Pyrophosphate In Water, Kwaku Twum, Seyed Iraj Sadraei, Jordan Feder, S. Maryamdokht Taimoory, Kari Rissanen, John F. Trant, Ngong Kodiah Beyeh

Chemistry and Biochemistry Publications

N-Alkyl ammonium resorcinarene chloride receptors, NARX4, have been shown to act as high-sensitivity detectors of pyrophosphate (PPi), a biomarker of disease, in aqueous media through the chloride-to-PPi exchange [NAR(Cl)4 to NARPPi]. The nature of the anion of the macrocyclic NARX4 (X = Cl−, Br−, triflate OTf−) receptor greatly influences the PPi-affinity in aqueous media. The binding affinity for [NAR (Cl)4] is 3.61 × 105 M−1, while the NAR (Br)4 and NAR (OTf)4 show stronger binding of 5.30 × 105 M−1, and 6.10 × 105 M−1, respectively. The effects of upper rim ammonium cation, –N+H2R substituents (R = 3-hydroxypropyl, cyclohexyl, …