Medicinal-Pharmaceutical Chemistry Commons^™

Multiomics Approach Captures Hepatic Metabolic Network Altered By Chronic Ethanol Administration, Isin Tuna Sakallioglu, Bridget Tripp, Jacy Kubik, Carol A. Casey, Paul G. Thomes, Robert Powers

Chemistry Department: Faculty Publications

Using a multiplatform and multiomics approach, we identified metabolites, lipids, proteins, and metabolic pathways that were altered in the liver after chronic ethanol administration. A functional enrichment analysis of the multiomics dataset revealed that rats treated with ethanol experienced an increase in hepatic fatty acyl content, which is consistent with an initial development of steatosis. The nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC-MS) metabolomics data revealed that the chronic ethanol exposure selectively modified toxic substances such as an increase in glucuronidation tyramine and benzoyl; and a depletion in cholesterol-conjugated glucuronides. Similarly, the lipidomics results revealed that ethanol …

Uv-Light-Tunable P-/N-Type Chemiresistive Gas Sensors Based On Quasi-1d Tis3 Nanoribbons: Detection Of Isopropanol At Ppm Concentrations, Victor V. Sysoev, Andrey V. Lashkov, Alexey Lipatov, Ilya A. Plugin, Michael Bruns, Dirk Fuchs, Alexey S. Varezhnikov, Mustahsin Adib, Martin Sommer, Alexander Sinitskii

Chemistry Department: Faculty Publications

The growing demand of society for gas sensors for energy-efficient environmental sensing stimulates studies of new electronic materials. Here, we investigated quasi-one-dimensional titanium trisulfide (TiS₃) crystals for possible applications in chemiresistors and on-chip multisensor arrays. TiS₃ nanoribbons were placed as a mat over a multielectrode chip to form an array of chemiresistive gas sensors. These sensors were exposed to isopropanol as a model analyte, which was mixed with air at low concentrations of 1–100 ppm that are below the Occupational Safety and Health Administration (OSHA) permissible exposure limit. The tests were performed at room temperature (RT), as …

Threonine Phosphorylation Of An Electrochemical Peptide-Based Sensor To Achieve Improved Uranyl Ion Binding Affinity, Channing C. Thompson, Rebecca Lai

Chemistry Department: Faculty Publications

We have successfully designed a uranyl ion (U(VI)-specific peptide and used it in the fabrication of an electrochemical sensor. The 12-amino acid peptide sequence, (n) DKDGDGYIpTAAE (c), originates from calmodulin, a Ca(II)-binding protein, and contains a phosphothreonine that enhances the sequence’s affinity for U(VI) over Ca(II). The sensing mechanism of this U(VI) sensor is similar to other electrochemical peptide-based sensors, which relies on the change in the flexibility of the peptide probe upon interacting with the target. The sensor was systematically characterized using alternating current voltammetry (ACV) and cyclic voltammetry. Its limit of detection was 50 nM, which is lower …

Fine Tuning The Pore Surface In Zirconium Metal−Organic Frameworks For Selective Ethane/Ethylene Separation, Yuchen Hu, Yanshu Shi, Yi Xie, Rebecca Shu Hui Khoo, Christian Fiankor, Xu Zhang,, Banglin Chen, Jian Zhang

Chemistry Department: Faculty Publications

Ethylene is an important chemical feedstock for production of polymers and high-value organic chemicals, and yet its conventional purification process is plagued with high consumption of energy. Metal−organic frameworks (MOFs) provide a suitable adsorption platform for selective ethane/ ethylene separation thanks to their structural diversity, tunable pore characteristics, designable pore sizes, and high pore volumes. Although there are empirical design rules like avoiding open metal sites and creating nonpolar pore surfaces for development of adsorptive MOFs, it is still challenging to design robust MOFs that can realize direct ethane-selective separation. Herein, we systematically designed and synthesized three Zr-MOFs based on …

Leveraging The Structure Of Dnaja1 To Discover Novel Potential Pancreatic Cancer Therapies, Heidi E. Roth, Aline De Lima Leite, Nicolas Y. Palermo, Robert Powers

Chemistry Department: Faculty Publications

Pancreatic cancer remains one of the deadliest forms of cancer with a 5-year survival rate of only 11%. Difficult diagnosis and limited treatment options are the major causes of the poor outcome for pancreatic cancer. The human protein DNAJA1 has been proposed as a potential therapeutic target for pancreatic cancer, but its cellular and biological functions remain unclear. Previous studies have suggested that DNAJA10s cellular activity may be dependent upon its protein binding partners. To further investigate this assertion, the first 107 amino acid structures of DNAJA1 were solved by NMR, which includes the classical J-domain and its associated linker …

Ai Protein Structure Prediction-Based Modeling And Mutagenesis Of A Protostome Receptor And Peptide Ligands Reveal Key Residues For Their Interaction, Shi-Qi Guo, Ya-Dong Li, Ping Chen, Guo Zhang, Hui-Ying Wang, Hui-Min Jiang, Wei-Jia Liu, Ju-Ping Xu, Xue-Ying Ding, Ping Fu, Ke Yu, Hai-Bo Zhou, James W. Checco, Jian Jing

Chemistry Department: Faculty Publications

The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide–receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides …

Meta-Analysis Reveals Both The Promises And The Challenges Of Clinical Metabolomics, Heidi E. Roth, Robert Powers

Chemistry Department: Faculty Publications

Clinical metabolomics is a rapidly expanding field focused on identifying molecular biomarkers to aid in the efficient diagnosis and treatment of human diseases. Variations in study design, metabolomics methodologies, and investigator protocols raise serious concerns about the accuracy and reproducibility of these potential biomarkers. The explosive growth of the field has led to the recent availability of numerous replicate clinical studies, which permits an evaluation of the consistency of biomarkers identified across multiple metabolomics projects. Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death and has the lowest five-year survival rate primarily due to the lack of an …

Editorial: Expansion Of The Genetic Code: Unnatural Amino Acids And Their Applications, Subhendu Sekhar Bag, Ishu Saraogi, Jiantao Guo

Chemistry Department: Faculty Publications

No abstract provided.

Nmr And Metabolomics—A Roadmap For The Future, David S. Wishart, Leo L. Cheng, Valérie Copié, Arthur S. Edison, Hamid R. Eghbalnia, Jeffrey C. Hoch, Goncalo J. Gouveia, Wimal Pathmasiri, Robert Powers, Tracey B. Schock, Lloyd W. Sumner, Mario Uchimiya

Chemistry Department: Faculty Publications

Metabolomics investigates global metabolic alterations associated with chemical, biological, physiological, or pathological processes. These metabolic changes are measured with various analytical platforms including liquid chromatography-mass spectrometry (LC-MS), gas chromatographymass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). While LC-MS methods are becoming increasingly popular in the field of metabolomics (accounting for more than 70% of published metabolomics studies to date), there are considerable benefits and advantages to NMR-based methods for metabolomic studies. In fact, according to PubMed, more than 926 papers on NMR-based metabolomics were published in 2021—the most ever published in a given year. This suggests that NMR-based metabolomics …

Negative Photoresponse In Ti3C2TX Mxene Monolayers, Nataliia S. Vorobeva, Saman Bagheri, Angel Torres, Alexander Sinitskii

Chemistry Department: Faculty Publications

Two-dimensional transition metal carbides, nitrides, and carbonitrides, collectively known as MXenes, are finding numerous applications in many different areas, including optoelectronics and photonics, but there is limited information about their intrinsic photoresponse. In this study, we investigated the visible and near-infrared range photoresponse of Ti₃C₂T_x, the most popular MXene material to date. The electrical measurements were performed on devices based on individual monolayer Ti₃C₂T_x MXene flakes, which were characterized by a variety of microscopic and spectroscopic methods. For MXene devices with different electrode layouts, the current reproducibly decreased under …

Characterization Of Three-Dimensional Fractional Viscoelastic Models Through Complex Modulus Analysis And Polar Decomposition, Avradip Ghosh, Avinash Kumar Both, Chin Li Cheung

Chemistry Department: Faculty Publications

Soft materials such as gels, elastomers, and biological tissues have diverse applications in nature and technology due to their viscoelastic nature. These soft materials often exhibit complex rheology and display elastic and viscous characteristics when undergoing deformation. In recent years, fractional calculus has emerged as a promising tool to explain the viscoelastic behavior of soft materials. Scalar constants are primarily used to quantify viscoelastic elements such as springs and dashpots. However, in three-dimensional (3D) space, not all materials show the same elastic or viscoelastic properties in all directions, especially under elastic/viscoelastic wave propagation (or anisotropy). Though previously reported studies on …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

Multiplexed Monitoring Of Neurochemicals Via Electrografting- Enabled Site-Selective Functionalization Of Aptamers On Field-Effect Transistors, Zan Gao, Guangfu Wu, Yang Song, Huijie Li, Yuxuan Zhang, Michael J. Schneider, Yingqi Qiang, Jackson Kaszas, Zhengyan Weng, He Sun, Bryan D. Huey, Rebecca Lai, Yi Zhang

Chemistry Department: Faculty Publications

Neurochemical corelease has received much attention in understanding brain activity and cognition. Despite many attempts, the multiplexed monitoring of coreleased neurochemicals with spatiotemporal precision and minimal crosstalk using existing methods remains challenging. Here, we report a soft neural probe for multiplexed neurochemical monitoring via the electrografting-assisted site-selective functionalization of aptamers on graphene field-effect transistors (G-FETs). The neural probes possess excellent flexibility, ultralight mass (28 mg), and a nearly cellular-scale dimension of 50 μm × 50 μm for each G-FET. As a demonstration, we show that G-FETs with electrochemically grafted molecular linkers (−COOH or −NH2) and specific aptamers can be used …

Asymmetrical Spectral Continuum Between Anti-Stokes And Stokes Scattering Revealed In Low-Frequency Surface-Enhanced Raman Spectroscopy, Shuo Sun, Dhanusha T.N. Rathnayake, Yinsheng Guo

Chemistry Department: Faculty Publications

An asymmetrical spectral continuum is observed in low-frequency surface-enhanced Raman spectroscopy (LF-SERS) in the terahertz (THz) region. This background continuum appears as a flat baseline in the Stokes side and a slope in the anti-Stokes side. Analysis shows this asymmetry originates from the different scaling of anti-Stokes and Stokes scattering with respect to the Bose−Einstein distribution. Such asymmetry is readily visible, under room temperature, in the low-frequency THz spectral range. Accounting for this spectral intensity asymmetry reveals the intrinsic continuum background of electronic origin, differing from local normal modes and collective relaxational motions. We also describe a numerical method, independent …

Noncanonical Amino Acid Mutagenesis In Response To Recoding Signal-Enhanced Quadruplet Codons, Yan Chen, Xinyuan He, University Of Nebraska-Lincoln, Kun Liu, Tian Gao, Wei Niu, Jiantao Guo

Chemistry Department: Faculty Publications

While amber suppression is the most common approach to introduce noncanonical amino acids into proteins in live cells, quadruplet codon decoding has potential to enable a greatly expanded genetic code with up to 256 new codons for protein biosynthesis. Since triplet codons are the predominant form of genetic code in nature, quadruplet codon decoding often displays limited efficiency. In this work, we exploited a new approach to significantly improve quadruplet UAGN and AGGN (N = A, U, G, C) codon decoding efficiency by using recoding signals imbedded in mRNA. With representative recoding signals, the expression level of mutant proteins containing …

Advanced Cnc/Peg/Pdmaa Semi-Ipn Hydrogel For Drug Delivery Management In Wound Healing, Samia Afrin, Md. Shahruzzaman, Papia Haque, Md. Sazedul Islam, Shafiul Hossain, Taslim Ur Rashid, Tanvir Ahmed, Makoto Takafuji, Mohammed Mizanur Rahman

Chemistry Department: Faculty Publications

A Semi Interpenetrating Polymer Network (semi-IPN) hydrogel was prepared and loaded with an antibiotic drug, gentamicin, to investigate the wound healing activity of this system. The semi-IPN hydrogel was synthesized by combining natural polymer cellulose nanocrystal (CNC) and synthetic polymer polyethylene glycol (PEG) and poly (N,N0-dimethyl acrylamide) (PDMAA), which was initially added as a monomer dimethyl acrylamide (DMAA). CNC was prepared from locally obtained jute fibers, dispersed in a PEG-NaOH solvent systemand then mixed with monomer DMAA, where polymerization was initiated by an initiator potassium persulphate (KPS) and cross-linked by N,N0-methylenebisacrylamide (NMBA). The size, morphology, biocompatibility, antimicrobial activity, thermal and …

1st Place Contest Entry: Designing Hollow Nanogels For Drug Delivery Applications, Mo Hijazi

Kevin and Tam Ross Undergraduate Research Prize

This is Mo Hijazi's submission for the 2022 Kevin and Tam Ross Undergraduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on hollow-core nanogels.

Mo is a second-year student at Chapman University, majoring in Biological Sciences. Their faculty mentor is Dr. Molla Islam.

Synthesis And Evaluation Of 11c-Labeled Triazolones As Probes For Imaging Fatty Acid Synthase Expression By Positron Emission Tomography, James M. Kelly, Thomas M. Jeitner, Nicole N. Waterhouse, Wenchao Qu, Ethan J. Linstad, Banafshe Samani, Clarence Williams Jr., Anastasia Nikolopoulou, Alejandro Amor-Coarasa, Stephen G. Dimagno, John W. Babich

Chemistry Department: Faculty Publications

Cancer cells require lipids to fulfill energetic, proliferative, and signaling requirements. Even though these cells can take up exogenous fatty acids, the majority exhibit a dependency on de novo fatty acid synthesis. Fatty acid synthase (FASN) is the rate-limiting enzyme in this process. Expression and activity of FASN is elevated in multiple cancers, where it correlates with disease progression and poor prognosis. These observations have sparked interest in developing methods of detecting FASN expression in vivo. One promising approach is the imaging of radiolabeled molecular probes targeting FASN by positron emission tomography (PET). However, although [¹¹C]acetate uptake by …

Chemical Reversible Crosslinking Enables Measurement Of Rna 3d Distances And Alternative Conformations In Cells, Ryan Van Damme, Kongpan Li, Minjie Zhang, Jianhui Bai, Wilson H. Lee, Joseph D. Yesselman, Zhipeng Lu, Willem A. Velema

Chemistry Department: Faculty Publications

Three-dimensional (3D) structures dictate the functions of RNA molecules in a wide variety of biological processes. However, direct determination of RNA 3D structures in vivo is difficult due to their large sizes, conformational heterogeneity, and dynamics. Here we present a method, Spatial 2′-Hydroxyl Acylation Reversible Crosslinking (SHARC), which uses chemical crosslinkers of defined lengths to measure distances between nucleotides in cellular RNA. Integrating crosslinking, exonuclease (exo) trimming, proximity ligation, and high throughput sequencing, SHARC enables transcriptome-wide tertiary structure contact maps at high accuracy and precision, revealing heterogeneous RNA structures and interactions. SHARC data provide constraints that improves Rosetta-based RNA 3D …

Decomposition Of Organic Peroxides And Hydrogen Peroxide By The Iron Thiolates And Related Complexes, Patrick H. Dussault, Andrew Olson

Chemistry Department: Faculty Publications

Disclosed herein is a method of reducing or disproportionating peroxide, comprising combining an organic chalcogenide, an iron salt, and the peroxide in the presence of an additional reductant, which can be the organic chalcogenide. The method can be used to, e.g., prepare alcohols from peroxides and to disproportionate hydrogen peroxide into water and oxygen.

Effects Of Long-Term Fluoride Exposure Are Associated With Oxidative Biochemistry Impairment And Global Proteomic Modulation, But Not Genotoxicity, In Parotid Glands Of Mice, Giza Hellen Nonato Mirandai, Leidiane Alencar De Oliveira Lima, Leonardo Oliveira Bittencourt, Sa´Vio Monteiro Dos Santos, Michel Platini Caldas De Souza, Lygia Sega Nogueira, Edivaldo Herculano Corrêa De Oliveira, Marta Chagas Monteir, Aline Dionizio, Aline Lima Leite, Juliano Pelim Pessan, Juliano Pelim Pessan, Marı´Lia Afonso Rabelo Buzalaf, Rafael Rodrigues Limai

Chemistry Department: Faculty Publications

Fluoride has become widely used in dentistry because of its effectiveness in caries control. However, evidence indicates that excessive intake interferes with the metabolic processes of different tissues. Thus, this study aimed to investigate the effects of long-term exposure to F on the parotid salivary gland of mice, from the analysis of oxidative, proteomic and genotoxic parameters.

The animals received deionized water containing 0, 10 or 50 mg/L of F, as sodium fluoride, for 60 days. After, parotid glands were collected for analysis of oxidative biochemistry, global proteomic profile, genotoxicity assessment and histopathological analyses.

The results revealed that exposure to …

Web-Based Platform For Analysis Of Rna Folding From High Throughput Chemical Probing Data, Christopher Jurich, Amir Brivanlou, Silvi Rouskin, Joseph D. Yesselman

Chemistry Department: Faculty Publications

RNA structures play critical roles in regulating gene expression across all domains of life and viruses. Chemical probing methods coupled with massively parallel sequencing have revolutionized the RNA structure field by enabling the assessment of many structures in their native, physiological context. Previously, we developed Dimethyl-Sulfate-based Mutational Profiling and Sequencing (DMS-MaPseq), which uses DMS to label the Watson-Crick face of open and accessible adenine and cytosine bases in the RNA. We used this approach to determine the genome-wide structures of HIV-1 and SARS-CoV-2 in infected cells, which permitted uncovering new biology and identifying therapeutic targets. Due to the simplicity and …

Peptidomics Analysis Reveals Changes In Small Urinary Peptides In Patients With Interstitial Cystitis/Bladder Pain Syndrome, Md Shadman Ridwan Abid, Haowen Qiu, Bridget Tripp, Aline De Lima Leite, Heidi E. Roth, Jiri Adamec, Robert Powers, James W. Checco

Chemistry Department: Faculty Publications

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating pain disorder of the bladder and urinary tract with poorly understood etiology. A definitive diagnosis of IC/BPS can be challenging because many symptoms are shared with other urological disorders. An analysis of urine presents an attractive and non-invasive resource for monitoring and diagnosing IC/BPS. The antiproliferative factor (APF) peptide has been previously identified in the urine of IC/BPS patients and is a proposed biomarker for the disorder. Nevertheless, other small urinary peptides have remained uninvestigated in IC/BPS primarily because protein biomarker discovery efforts employ protocols that remove small endogenous peptides. …

Developing A New Treatment For Superficial Fungal Infection Using Antifungal Collagen-Hsaf Dressing, Jing Zhong, Xiayi Yan, Xin Zuo, Xuan Zhao, Jiahui Yang, Qin Dou, Lulu Peng, Yuxiang Zhu, Yichen Xiao, Zeran Bian, Dalian He, Qiushuang Xu, Stephen Wright, Yaoyao Li, Liangcheng Du, Yan Wang, Jin Yuan

Chemistry Department: Faculty Publications

Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine-derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction …