Chemicals and Drugs Commons^™

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations & Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan

School of Medicine Faculty Publications

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)₅C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl₃ with [(WR)₅C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B₃and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B₃are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD⁺decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD⁺levels. BHB is naturally produced by the body when individuals fast …

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Towards Stable Electrochemical Sensing For Wearable Wound Monitoring, Sohini Roychoudhury

FIU Electronic Theses and Dissertations

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights …

Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to …

Effect Of Tyrosine On The Productivity Of Pc12 Cells By Measuring Extracellular Atp Release, Sabrina Burkholder, Mary Rapmund, David Fogel, Jon Flees

Student Scholar Symposium Abstracts and Posters

Given the challenge to “reverse-engineer the brain”, our group tried to address the problems of a lack of long term focus and attention span. Tyrosine was determined to aid in mental focus and brain productivity as it is a precursor to the neurotransmitter Dopamine. Given that Tyrosine is naturally occurring in the body, it is preferable to add to the body, whereas a substance like Adderall has negative effects, including increased heart rate that, over time, can cause cardiovascular damage. Drawing connections between in increase ATP and an increased ability to focus and perform under stress, extracellular ATP secretion of …

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase …

Leucine Supplementation In Cuprizone-Induced Oligodendrocyte Toxicity, Michael Ley

Williams Honors College, Honors Research Projects

Cuprizone is a copper chelator that induces demyelination in the central nervous system when fed to mice. This compound is thought to target Complex IV and disrupt mitochondrial metabolism leading to loss of myelin-producing oligodendrocytes. In this proposal, we further examine the chemical and toxicological properties of cuprizone. Immunofluorescence imaging and microarray data on MO3.13 cells treated with cuprizone revealed the possibility of alterations in lysosomal function, as well as mitochondrial disruption via mTOR and Electron Transport Chain (ETC) related pathways. Cell viability assays conducted suggest that addition of Branched-Chain Amino Acids, most commonly used from literature, leucine, can increase …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions.

Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis–Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot.

Microsomal CYP2D exhibited high affinity and low capacity, compared with the mitochondrial CYP2D that had a much lower (∼50-fold) affinity but a higher (∼six-fold) …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the …

Oxcarbazepine Overdose In A Polysubstance Related Suicide, Melissa Beals, Robert J. Krumsick, C. Clinton Frazee Iii, Lindsey J. Haldiman, Uttam Garg

Posters

Introduction
Oxcarbazepine is a derivative of carbamazepine that is used primarily in the treatment of epilepsy, and experimentally as a mood-stabilizer in adjunctive therapy for the treatment of bipolar disorder. Oxcarbazepine is converted through oxidation to its pharmacologically active metabolite 10-OH-Carbazepine, which is thought to be responsible for most of the anticonvulsant action of the drug. Adverse effects of oxcarbazepine are generally dose-dependent and may include fatigue, somnolence, dizziness, diplopia, nystagmus, and ataxia. Additive sedative effects have been noted when oxcarbazepine is used in combination with other CNS depressionproducing medications. Furthermore, oxcarbazepine and 10-OH-Carbazepine are powerful CYP2C19 inhibitors, potentially increasing …

Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt

Pharmacy Faculty Articles and Research

Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified and …

Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt

Electronic Theses and Dissertations

Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of …

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the …

30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman

Celebration of Learning

There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 and …

Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda

Pharmacy Faculty Articles and Research

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune responses, cell death …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …