Amino Acids, Peptides, and Proteins Commons^™

In-Silico Analysis Of Interacting Pathways Through Kim-1 Protein Interaction In Diabetic Nephropathy, Fatima Abid, Z Rubab, Syeda Sadia Fatima, A Qureshi, Arfa Azhar, A Jafri

Department of Biological & Biomedical Sciences

Background: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1.
Methods: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

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 …

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani

Mathematics, Physics, and Computer Science Faculty Articles and Research

At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection …

A Case Report On Causes Of Covid-19 Induced Psychosis And Treatments, Jennifer Pires, Steven Sarner

Stratford Campus Research Day

COVID-19 is a viral infection that is caused by an RNA virus in a subfamily of Coronaviridae named severe acute respiratory syndrome (SARS CoV 2). The family also includes severe acute respiratory syndrome coronavirus (SARS CoV) and middle east respiratory syndrome coronavirus (MERS CoV) which have previously been shown to cause respiratory symptoms and psychosis with immunoreactivity to IgG.

Case Report: Octreotide Associated Hyperkalemia, Darren Finn, Eric Maddock, James Espinosa, Andrew Caravello, Alan Lucerna, Henry Schuitema

Stratford Campus Research Day

78-year-old female with past medical history of acromegaly status post pituitary adenoma status post resection presents to the emergency department with abdominal pain. ED workup was not significant for any acute intra-abdominal abnormalities; however, incidental finding of hyperkalemia was pertinent to the visit. Patient was treated in the ED for her condition but her potassium levels remained elevated despite repeated saline infusions. Patient was ultimately admitted to the hospital where it was discovered that she had recently been switched from octreotide injections to an oral somatostatin analogue Mycapssa. We believe that this patient’s hyperkalemia was caused by octreotide-induced insulin suppression …

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Undergraduate Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) And Proteomic Evaluation Of Heparin-Binding Proteins From Ajwain (Trachyspermum Ammi) Seeds, Saud Alshammari

Pharmaceutical Sciences (PhD) Dissertations

Trachyspermum ammi, commonly known as ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered. The present study demonstrated the antiproliferative activity of ajwain nsLTP1 in MCF-7, AsPC-1, and MCF10A cell lines and its structural stability in human serum and high-temperature conditions. The antiproliferative activity of ajwain nsLTP1 was evaluated in MCF-7 and AsPC-1 cell lines using an MTT assay. Annexin V-FITC and PI staining were used to detect the …

Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, Michael Mckeever

Dissertations

Amphiphiles play important roles in nature. These molecules contain both hydrophilic and hydrophobic regions, leading to some astonishing properties. The lipid bilayer of the cell membrane is a fascinating organization of amphiphilic phospholipids. Natural and synthetic amphiphiles, such as antimicrobial peptides, interact with the cell membrane. Such interactions can impact transport of molecules across the cell membrane, disrupting cell functions. In this work, a library of tryptophan-containing amphiphiles was synthesized and their antimicrobial properties were explored.

First, a library of bis(tryptophan) amphiphiles was synthesized. Preparation included a coupling reaction of a diamine with tryptophan residues, via their carboxy-termini, at …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Bis-Cinnamamide Derivatives As Ape/Ref-1 Inhibitors For The Treatment Of Human Melanoma, Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlain, Keykavous Parang, Sun Yang

Pharmacy Faculty Articles and Research

Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed. We further synthesized compound …

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) …

Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …

Quadruped Gait And Regulation Of Apoptotic Factors In Tibiofemoral Joints Following Intra-Articular Rhprg4 Injection In Prg4 Null Mice, Daniel S. Yang, Edward E. Dickerson, Ling X. Zhang, Holly Richendrfer, Padmini N. Karamchedu, Gary A. Badger, Tannin A. Schmidt, Alger M. Fredericks, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4^−/− (N = 44) mice of both sexes were injected with rhPRG4 …