Greer Studies, Teaches How To Improve Medicines, 2018 CUNY Bernard M Baruch College
Greer Studies, Teaches How To Improve Medicines, Aldemaro Romero Jr.
Publications and Research
“As a child, I was interested in asking questions. Like why different substances work the way they do and why they have some effect on our bodies. I was fascinated by hydrogen-peroxide and how it decomposes when you pour it on the wound. I would ask why it happens, what is the reason?” That’s how Dr. Edyta Greer explains how she became interested in science. A native of Poland, Greer received her master’s from Warsaw University and her doctorate from the Graduate Center of the City University of New York. Today she is an associate professor in the ...
Preparation Of Polymeric Materials From Bio-Renewable Sources, 2018 Rowan University
Preparation Of Polymeric Materials From Bio-Renewable Sources, Jason Douglas Smith
Theses and Dissertations
The focus of this project was to develop methodologies for the preparation of novel polymeric materials from bio-renewable sources. In order to complete this task we needed (a) unfettered access to bio-based materials and ways to convert them to value needed chemicals, as well as, (b) reaction protocols that would allow greater diversity during the synthesis of polymeric compounds so as to affect the properties of these materials.
Our research group has a background in converting plant-based materials like cellulose into value added chemicals employing catalytic reactions. The polymerization of these monomers was then conducted utilizing the Baylis-Hillman reaction. The ...
Comparison Of Partially And Fully Chemically-Modified Sirna In Conjugate-Mediated Delivery In Vivo, 2018 University of Massachusetts Medical School
Comparison Of Partially And Fully Chemically-Modified Sirna In Conjugate-Mediated Delivery In Vivo, Matthew R. Hassler, Anton A. Turanov, Julia F. Alterman, Reka A. Haraszti, Andrew H. Coles, Maire F. Osborn, Dimas Echeverria, Mehran Nikan, William E. Salomon, Loic Roux, Bruno M. D. C. Godinho, Sarah M. Davis, David V. Morrissey, Phillip D. Zamore, S. Ananth Karumanchi, Melissa J. Moore, Neil Aronin, Anastasia Khvorova
Open Access Articles
Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bio-conjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides). Here, we compare partially and fully chemically modified siRNAs in conjugate mediated delivery. We show that fully modified siRNAs are retained at 100x greater levels in various ...
Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, 2018 The Graduate Center, City University of New York
Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, Michael P. D'Erasmo
All Dissertations, Theses, and Capstone Projects
Historically, natural products have provided unique research opportunities and challenges for organic synthesis, chemical biology, and medicinal chemistry due to their molecular complexity and effects on physiological systems. The total synthesis of natural products has not only produced novel reaction methods and strategies capable of efficiently generating complex structural motifs but also granted access to sufficient quantities of otherwise scarce natural product material for clinical evaluation. These synthetic efforts have facilitated the formation of a transdisciplinary partnership between chemistry, biology, and medicine that has been paramount in elucidating the chemical and pharmaceutical utility of natural products. Chapter I of this ...
A High Throughput Approach For The Generation Of Orthogonally Interacting Protein Pairs, 2018 University of Nebraska-Lincoln
A High Throughput Approach For The Generation Of Orthogonally Interacting Protein Pairs, Justin Lawrie, Xi Song, Wei Niu, Jiantao Guo
Faculty Publications -- Chemistry Department
In contrast to the nearly error-free self-assembly of protein architectures in nature, artificial assembly of protein complexes with pre-defined structure and function in vitro is still challenging. To mimic nature’s strategy to construct pre-defined three-dimensional protein architectures, highly specific proteinprotein interacting pairs are needed. Here we report an effort to create an orthogonally interacting protein pair from its parental pair using a bacteria-based in vivo directed evolution strategy. This high throughput approach features a combination of a negative and a positive selection. The newly developed negative selection from this work was used to remove any protein mutants that retain ...
Synthesis And Functionalization Of Virus-Mimicking Cationic Block Copolymers With Pathogen-Associated Carbohydrates As Potential Vaccine Adjuvants, J. R. Adams, M. Goswami, N. L.B. Pohl, Surya K. Mallapragada
Surya K. Mallapragada
We report the synthesis of a family of amphiphilic pentablock polymers with different cationic blocks and with controlled architectures as potential vaccine carriers for subunit vaccines. The temperature and pH-dependent micellization and gelation of these pentablock copolymers can provide a depot for sustained protein and gene delivery. The amphiphilic central triblock promotes cellular endocytosis, good gene delivery and has been used effectively as a vaccine adjuvant. The pentablock copolymer outer blocks condense DNA spontaneously as a result of electrostatic interactions for sustained combinational therapy. This family of polymers with different cationic groups was evaluated based on DNA complexation-ability and cytotoxicity ...
E‑Cigarette Airflow Rate Modulates Toxicant Profiles And Can Lead To Concerning Levels Of Solvent Consumption, 2018 Portland State University
E‑Cigarette Airflow Rate Modulates Toxicant Profiles And Can Lead To Concerning Levels Of Solvent Consumption, Tetiana Korzun, Maryana Lazurko, Tetiana Korzun, Ian Munhenzva, Kelley Barsanti, Yilin Huang, R. Paul Jensen, Jorge O. Escobedo, Wentai Luo, David H. Peyton, Robert M. Strongin
Chemistry Faculty Publications and Presentations
Electronic cigarettes enabling enhanced airflow have grown in popularity in recent years. The objective of this study is to show that flow rates modulate the levels of specific aerosol toxicants produced in electronic cigarettes. Flow rates used in various laboratory investigations involving e-cigarettes have varied widely to date, and can thus promote interlaboratory variability in aerosol product profiles. The thermal decomposition of hydroxyacetone and glycolaldehyde is less favorable at lower temperatures, supporting the observations of these products at higher flow rates/lower heating coil temperatures. Higher temperatures promote the formation of acetaldehyde from hydroxyacetone and formaldehyde from both hydroxyacetone and ...
Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, 2017 Harvard Medical School
Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, Yuval Avnir, Kristina L. Prachanronarong, Shurong Hou, Brendan J. Hilbert, Markus-Frederik Bohn, Timothy F. Kowalik, Robert W. Finberg, Jennifer P. Wang, Nese Kurt Yilmaz, Celia A. Schiffer, Wayne A. Marasco
Schiffer Lab Publications
The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 ...
Green Chemistry Oxidative Modification Of Peptoids Utilizing Bleach And Tempo, 2017 University of Arkansas, Fayetteville
Green Chemistry Oxidative Modification Of Peptoids Utilizing Bleach And Tempo, Jesse Leland Roberts
Theses and Dissertations
Biotherapeutic drugs, derived from biological molecules such as proteins and DNA, are becoming an integral and exceptionally critical aspect of modern medicine. Compared to common pharmaceutical drugs, biotherapeutics are much larger in size and have greater target specificity, allowing them to treat many chronic diseases ranging from cancer to rheumatoid arthritis. The major issue with protein based therapeutics is that they readily undergo proteolysis, or enzymatic degradation, when administered through subcutaneous injections. Traditionally, biotherapeutic modification procedures have centered on the use of PEG derivatives. This process, called PEGylation, is unfavorable due to the increases in molecular weights of the proteins ...
Directed Self-Assembly Of Fluorescence Responsive Nanoparticles And Their Use For Real-Time Surface And Cellular Imaging., 2017 Royal College of Surgeons in Ireland
Directed Self-Assembly Of Fluorescence Responsive Nanoparticles And Their Use For Real-Time Surface And Cellular Imaging., Shane Cheung, Donal F. O'Shea
Pharmaceutical and Medicinal Chemistry Articles
Directed self-assemblies in water are known as the most efficient means of forming complex higher ordered structures in nature. Here we show a straightforward and robust method for particle assembly which utilises the amphiphilic tri-block co-polymer poloxamer-188 and a hydrophobic fluorophore as the two designer components, which have a built-in ability to convey spatial and temporal information about their surroundings to an observer. Templating of particle self-assembly is attributed to interactions between the fluorophore and hydrophobic segment of the poloxamer. Particle fluorescence in water is quenched but can be induced to selectively switch on in response to temperature, surface adsorption ...
Substituted Hydroxylamines As Nitrogen Transfer Reagents: Direct Synthetic Pathways To Structurally Rich Heteroatomic Scaffolds, Dylan John Quinn
Theses and Dissertations
Nitrogen is found in virtually all valuable chemical compounds. The abundance of atmospheric nitrogen however, is rendered inaccessible because of the strong N-N triple bond, ultimately preventing its practical utilization in synthetic organic synthesis. The development of powerful nitrogen transfer reagents, such as substituted hydroxylamine derivatives, have played an important role in the introduction of nitrogen into valuable chemical scaffolding.
Herein is reported the methodological development of synthetic nitrogen placement into a range of valuable heteroatomic compounds. This work shows that O-Substituted Hydroxylamine can be used to furnish small heteroatomic compounds, particularly nitriles. Whereas, N-Substituted Hydroxylamine can be employed to ...
Progress Toward Phidianidine Analogues Containing A 1,2,3-Triazole Ring, 2017 Coastal Carolina University
Progress Toward Phidianidine Analogues Containing A 1,2,3-Triazole Ring, David Laws Iii, Dillon King, Bryan H. Wakefield
Journal of the South Carolina Academy of Science
Phidianidines are a class of compound that has been extracted from the sea mollusk Phidianis militaris. These compounds have been shown to exhibit a variety of useful properties such as antihistamine effects, anti-cancer activity, agonism of the µ-opioid receptor and neuroprotection. The biological activities are thought to be caused by the 1,2,4- oxadiazole ring found within the molecule. The goal of this project is to synthesize analogues of phidianidine that contain a 1,2,3-triazole instead of the 1,2,4 oxadiazole ring using a method that will allow for other regions of the molecule to be changed ...
Ensemble-Based Modeling And Rigidity Decomposition Of Allosteric Interaction Networks And Communication Pathways In Cyclin-Dependent Kinases: Differentiating Kinase Clients Of The Hsp90-Cdc37 Chaperone, 2017 Chapman University
Ensemble-Based Modeling And Rigidity Decomposition Of Allosteric Interaction Networks And Communication Pathways In Cyclin-Dependent Kinases: Differentiating Kinase Clients Of The Hsp90-Cdc37 Chaperone, Gabrielle Stetz, Amanda Tse, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The overarching goal of delineating molecular principles underlying differentiation of protein kinase clients and chaperone-based modulation of kinase activity is fundamental to understanding activity of many oncogenic kinases that require chaperoning of Hsp70 and Hsp90 systems to attain a functionally competent active form. Despite structural similarities and common activation mechanisms shared by cyclin-dependent kinase (CDK) proteins, members of this family can exhibit vastly different chaperone preferences. The molecular determinants underlying chaperone dependencies of protein kinases are not fully understood as structurally similar kinases may often elicit distinct regulatory responses to the chaperone. The regulatory divergences observed for members of CDK ...
Selective Targeting Of Bromodomains Of The Bromodomain-Phd Fingers Family Impairs Osteoclast Differentiation, Julia C. Meier, Hanna Witwicka, Sung-Yong Hwang, Mark J. Birnbaum, Stefan Knapp
Open Access Articles
Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform and two pan-BRPF bromodomain inhibitors (OF-1, NI-57). The developed inhibitors displaced BRPF bromodomains from chromatin and did not inhibit cell growth and proliferation. Intriguingly, the inhibitors impaired RANKL-induced differentiation of primary murine bone marrow cells and human primary monocytes into bone resorbing osteoclasts by specifically repressing transcriptional ...
Platinum(Iv) Oxaliplatin-Peptide Conjugates Targeting Memhsp70+ Phenotype In Colorectal Cancer Cells., 2017 Royal College of Surgeons in Ireland
Platinum(Iv) Oxaliplatin-Peptide Conjugates Targeting Memhsp70+ Phenotype In Colorectal Cancer Cells., Aoife M. Mckeon, Janis Noonan, Marc Devocelle, Brona M. Murphy, Darren M. Griffith
Pharmaceutical and Medicinal Chemistry Articles
Novel Pt(iv) tumour penetrating peptide (TPP) conjugates are reported. They are the first example of metallodrugs to target a membrane bound heat shock protein 70 positive (memHSP70+) phenotype in cancer cells. The conjugates exhibit superior cytotoxicity as compared to oxaliplatin alone in Pt resistant colorectal cancer cells with relatively high memHSP70+ expression. Substitution of TPP in Pt(iv) peptide conjugates with scrambled peptide (ScP) essentially abolishes the observed cytotoxicity.
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, 2017 Rowan University
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, Lindsay Michelle Renn
Theses and Dissertations
The majority of chronic myeloid leukemia (CML) patients can be treated with and respond to imatinib mesylate (Gleevec). Imatinib is known to inhibit BCR-ABLl kinase activity, and is effective for the treatment of the majority of CML patients. Multiple mutations have been found in patients resistant to imatinib treatment, including many located in the BCR-ABLl tyrosine kinase domain (e.g. E255K and T315I). Matrine is a bioactive alkaloid from Sophora flavescens and has been shown to inhibit several types of cancers and is used in Chinese medicine. The goal of this study is to develop new matrine derivatives that inhibit ...
Toxicant Formation In Dabbing: The Terpene Story, 2017 Portland State University
Toxicant Formation In Dabbing: The Terpene Story, Jiries Meehan-Attrash, Wentai Luo, Robert M. Strongin
Chemistry Faculty Publications and Presentations
Inhalable, noncombustible cannabis products are playing a central role in the expansion of the medical and recreational use of cannabis. In particular, the practice of “dabbing” with butane hash oil has emerged with great popularity in states that have legalized cannabis. Despite their growing popularity, the degradation product profiles of these new products have not been extensively investigated. The study herein focuses on the chemistry of myrcene and other common terpenes found in cannabis extracts. Methacrolein, benzene, and several other products of concern to human health were formed under the conditions that simulated realworld dabbing. The terpene degradation products observed ...
Nonlinear Oscillatory Dynamics Of The Hardening Of Calcium Phosphate Bone Cements, 2017 Chapman University
Nonlinear Oscillatory Dynamics Of The Hardening Of Calcium Phosphate Bone Cements, Vuk Uskoković, Julietta V. Rau
Pharmacy Faculty Articles and Research
Here we report on the nonlinear, oscillatory dynamics detected in the evolution of phase composition during the setting of different calcium phosphate cements, two of which evolved toward brushite and one toward hydroxyapatite as the final product. Whereas both brushite-forming cements contained iondoped b-tricalcium phosphate as the initial phase, the zinc-containing one yielded scholzite as an additional phase during setting and the oscillations between these two products were pronounced throughout the entire 80 h setting period, long after the hardening processes was over from the mechanical standpoint. Oscillations in the copper-containing system involved the amount of brushite as the main ...
Crystal Engineering Of Active Pharmaceutical Ingredients With Low Aqueous Solubility And Bioavailability, 2017 The University of Western Ontario
Crystal Engineering Of Active Pharmaceutical Ingredients With Low Aqueous Solubility And Bioavailability, Jenna M. Skieneh
Electronic Thesis and Dissertation Repository
Approximately 75% of new molecular entities approved by the Food and Drug Administration (FDA) for use in the pharmaceutical industry are found to have poor aqueous solubility. This undesirable attribute leads to consequences such as higher doses required to reach therapeutic levels, greater vulnerability to food effects, lesser fraction absorbed in the small intestine and damage to the environment due to increased quantity of excretion. The addition of an excipient (i.e. a FDA approved inactive ingredient) to the molecular structure of an active pharmaceutical ingredient (API) through intermolecular bonding is of growing interest because the properties of the API ...
Development Of Entrapment Columns For The Study Of Affinity Based Analysis Of Drug-Protein Interactions, 2017 University of Nebraska-Lincoln
Development Of Entrapment Columns For The Study Of Affinity Based Analysis Of Drug-Protein Interactions, Shiden T. Azaria
Student Research Projects, Dissertations, and Theses - Chemistry Department
High-performance affinity chromatography (HPAC) is a type of liquid chromatography in which solutes are separated based on their binding to a stationary phase that is a biologically-related agent. Because of the strong and selective nature of many biological interactions, this method has already become a powerful technique for the purification and analysis of solutes that are complementary to the immobilized binding agent. Human serum albumin (HSA), the most abundant protein in the blood with concentrations of 35-50 mg/mL in serum, has interactions with many drugs, which can affect the absorption, distribution, metabolism and excretion of such agents.
The overall ...