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Medicinal-Pharmaceutical Chemistry Commons

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Fine-Tuning Interaction Between Aminoacyl-Trna Synthetase And Trna For Efficient Synthesis Of Proteins Containing Unnatural Amino Acids, Nanxi Wang, Tong Ju, Wei Niu, Jiantao Guo 2015 University of Nebraska-Lincoln

Fine-Tuning Interaction Between Aminoacyl-Trna Synthetase And Trna For Efficient Synthesis Of Proteins Containing Unnatural Amino Acids, Nanxi Wang, Tong Ju, Wei Niu, Jiantao Guo

Faculty Publications -- Chemistry Department

By using a directed evolution approach, we have identified aminoacyl-tRNA synthetase variants with significantly enhanced activity for the incorporation of unnatural amino acids into proteins in response to the amber nonsense codon in bacteria. We demonstrated that the optimization of anticodon recognition of tRNA by aminoacyltRNA synthetase led to improved incorporation efficiency that is unnatural amino acid-specific. The findings will facilitate the creation of an optimized system for the genetic incorporation of unnatural amino acids in bacteria.


Stretchable Conductive Composites For Use In Soft Devices, Joshua Aaron Lessing, Stephen A. Morin, George M. Whitesides 2015 Cambridge, MA

Stretchable Conductive Composites For Use In Soft Devices, Joshua Aaron Lessing, Stephen A. Morin, George M. Whitesides

Faculty Publications -- Chemistry Department

An elastically-deformable, conductive composite using elastomers and conductive fibers and simple fabrication procedures is provided. Conductive elastomeric composites offer low resistance to electrical current and are elastic over large (>25%) extensional strains. They can be easily interfaced/built into structures fabricated from elastomeric polymers.


Apparatus, Systems, And Methods For Modular Soft Robots, Stephen A. Morin, Sen Wai Kwok, Robert F. Shepherd, George M. Whitesides 2015 University of Nebraska - Lincoln

Apparatus, Systems, And Methods For Modular Soft Robots, Stephen A. Morin, Sen Wai Kwok, Robert F. Shepherd, George M. Whitesides

Faculty Publications -- Chemistry Department

Apparatus, Systems, and methods for providing modular soft robots are disclosed. In particular, the disclosed modular soft robot can include a flexible actuator having a plurality of molded flexible units. Each molded flexible unit can include a mechanical connector configured to provide a physical coupling to another molded flexible unit, and the plurality of molded flexible units are arranged to form an embedded fluidic channel. The modular soft robot can also include an inlet coupled to the embedded fluidic channel, where the inlet is configured to receive pressurized or depressurized fluid to inflate or deflate a portion of the flexible ...


Communication: Spectroscopic Consequences Of Proton Delocalization In Ochco+, Ryan C. Fortenberry, Qi Yu, John S. Mancini, Joel M. Bowman, Timothy J. Lee, T. Daniel Crawford, William F. Klemperer, Joseph S. Francisco 2015 Georgia Southern University

Communication: Spectroscopic Consequences Of Proton Delocalization In Ochco+, Ryan C. Fortenberry, Qi Yu, John S. Mancini, Joel M. Bowman, Timothy J. Lee, T. Daniel Crawford, William F. Klemperer, Joseph S. Francisco

Faculty Publications -- Chemistry Department

Even though quartic force fields (QFFs) and highly accurate coupled cluster computations describe the OCHCO+ cation at equilibrium as a complex between carbon monoxide and the formyl cation, two notable and typical interstellar and atmospheric molecules, the prediction from the present study is that the equilibrium C∞v structure is less relevant to observables than the saddle-point D∞h structure. This is the conclusion from diffusion Monte Carlo and vibrational self-consistent field/virtual state configuration interaction calculations utilizing a semi-global potential energy surface. These calculations demonstrate that the proton “rattle” motion (ν6) has centrosymmetric delocalization of the proton over ...


Ozonolysis Of Silyl Enol Ethers: Synthesis Of 3-Silyloxy-1,2-And 3-Alkyl-3-Silyloxy-1,2-Dioxolanes, Katrina Wilson 2015 University of Redlands

Ozonolysis Of Silyl Enol Ethers: Synthesis Of 3-Silyloxy-1,2-And 3-Alkyl-3-Silyloxy-1,2-Dioxolanes, Katrina Wilson

Undergraduate Honors Theses

Silyl enol ethers are important synthetic intermediates that are used in a variety of reactions. The ozonolysis of silyl enol ethers to anomalous 1,2-dioxolane products has not yet been fully been explored. Though the synthesis of silyl enol ethers from aldehydes, ketones, and esters is relatively straightforward, the most commonly used methods still require air- or moisture-sensitive conditions and/or the use of toxic solvents. We have shown that silyl enol ethers can be easily synthesized from aldehydes and ketones under mild conditions and with a straightforward workup procedure in good to excellent yields. We ozonolyzed these silyl enol ...


Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger 2015 Georgia Southern University

Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger

Electronic Theses and Dissertations

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.


Crystal Structure Of The Alcanivorax Borkumensis Ydah Transporter Reveals An Unusual Topology, Jani Reddy Bolla, Chih-Chia Su, Jared A. Delmar, Pattathil Radhakrishnan, Nitin Kumar, Tsung-Han Chou, Feng Long, Kanagalaghatta R. Rajashankar, Edward Yu 2015 Iowa State University

Crystal Structure Of The Alcanivorax Borkumensis Ydah Transporter Reveals An Unusual Topology, Jani Reddy Bolla, Chih-Chia Su, Jared A. Delmar, Pattathil Radhakrishnan, Nitin Kumar, Tsung-Han Chou, Feng Long, Kanagalaghatta R. Rajashankar, Edward Yu

Physics and Astronomy Publications

The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to ...


Structure And Function Of Neisseria Gonorrhoeae Mtrf Illuminates A Class Of Antimetabolite Efflux Pumps, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Tsung-Han Chou, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu 2015 Iowa State University

Structure And Function Of Neisseria Gonorrhoeae Mtrf Illuminates A Class Of Antimetabolite Efflux Pumps, Chih-Chia Su, Jani Reddy Bolla, Nitin Kumar, Pattathil Radhakrishnan, Feng Long, Jared A. Delmar, Tsung-Han Chou, Kanagalaghatta R. Rajashankar, William M. Shafer, Edward Yu

Physics and Astronomy Publications

Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to ...


Specific N-Glycans Of Hepatocellular Carcinoma Cell Surface And The Abnormal Increase Of Core-Α-1, 6-Fucosylated Triantennary Glycan Via N-Acetylglucosaminyltransferases-Iva Regulation, Huan Nie, Xia Liu, Yubao Zhang, Tingting Li, Chao Zhan, Wenjuan Huo, Anshun He, Yuanfei Yao, Yu Jin, Youpeng Qu, Xue-Long Sun, Yu Li 2015 Harbin Institute of Technology

Specific N-Glycans Of Hepatocellular Carcinoma Cell Surface And The Abnormal Increase Of Core-Α-1, 6-Fucosylated Triantennary Glycan Via N-Acetylglucosaminyltransferases-Iva Regulation, Huan Nie, Xia Liu, Yubao Zhang, Tingting Li, Chao Zhan, Wenjuan Huo, Anshun He, Yuanfei Yao, Yu Jin, Youpeng Qu, Xue-Long Sun, Yu Li

Chemistry Faculty Publications

Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC.


Peptide Drug Discovery: Innovative Technologies And Transformational Medicines, David J. Diller, Mark Jarosinski, Tomi K. Sawyer, Joseph Audie 2015 Sacred Heart University

Peptide Drug Discovery: Innovative Technologies And Transformational Medicines, David J. Diller, Mark Jarosinski, Tomi K. Sawyer, Joseph Audie

Chemistry & Physics Faculty Publications

Interest in peptide drug discovery is surging. In the past several years,numerous pharmaceutical and biotech companies have committed considerable resources to peptide-based drug discovery. In part,this is being fueled by an increasing recognition that peptide drugs combine many of the virtues of small molecules and proteins, while minimizing several of their drawbacks, and that peptides can potentially expand the druggable space to include intracellular, extracellular and membrane associated protein–protein interactions. Moreover, powerful new in vitro and in silico technologies and breakthroughs in our understanding of natural peptides have emerged that provide peptide chemists with the toolsand insights ...


Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce 2015 University of Akron Main Campus

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C2 substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by 1H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable ...


Synthesis And Anti-Proliferative Activity Of N,N’-Bis(Arylmethyl)Benzimidazolium Salts, Travis M. Williams 2015 University of Akron Main Campus

Synthesis And Anti-Proliferative Activity Of N,N’-Bis(Arylmethyl)Benzimidazolium Salts, Travis M. Williams

Williams Honors College, Honors Research Projects

A series of N,N’-bis(arylmethyl)benzimidazolium salts with hydrophilic and lipophilic substituents have been synthesized, characterized, and tested against select non-small cell cancer cell lines. Substituent variations on the imidazole ring have shown that lipophilicity and hydrophilicity can influence the imidazolium salts’ anti-proliferative activity and aqueous solubility.


Design, Synthesis, And Bio Relevant Applications Of Zwitterionic Amphiphilic Macromolecular Assemblies, Rajasekhar Reddy Rami Reddy 2015 Rajasekhar Reddy Rami Reddy

Design, Synthesis, And Bio Relevant Applications Of Zwitterionic Amphiphilic Macromolecular Assemblies, Rajasekhar Reddy Rami Reddy

Doctoral Dissertations

Supramolecular nanoassemblies capable of reducing non-specific interactions with biological macromolecules, such as proteins, are of great importance for various biological applications especially for targeted drug delivery therapeutics. Recently, zwitterionic materials have been shown to reduce non-specific interactions with biomolecules, owing both to their charge neutrality and their ability to form strong hydration layer around zwitterions via electrostatic interactions. This dissertation focuses on design, synthesis, thorough characterization, and applications of zwitterionic amphiphilic dendrimers and polymeric materials. Firstly, A new triazole-based zwitterionic moiety was conceived and incorporated as the hydrophilic functionality in facially amphiphilic dendrons. Self-assembly characteristics and the structural and functional ...


Stereocontrolled 1,2-Cis Glycosylation As The Driving Force Of Progress In Synthetic Carbohydrate Chemistry, Swati S. Nigudkar, Alexei V. Demchenko 2014 University of Missouri–St. Louis

Stereocontrolled 1,2-Cis Glycosylation As The Driving Force Of Progress In Synthetic Carbohydrate Chemistry, Swati S. Nigudkar, Alexei V. Demchenko

Alexei Demchenko

Recent developments in stereoselective 1,2-cis glycosylation that have emerged during the past decade are surveyed herein. For detailed coverage of the previous achievements in the field the reader is referred to our earlier reviews: A. V. Demchenko, Curr. Org. Chem., 2003, 7, 35–79 and Synlett, 2003, 1225–1240.


Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan 2014 Dow Europe GmbH

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification ...


The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung 2014 European Centre for the Validation of Alternative Methods

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the ...


Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino 2014 James Madison University

Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino

Masters Theses

The decline in the development of novel antimicrobials, combined with the misusage and over prescription of antibiotics, has contributed to the increasing prevalence of antimicrobial-resistant infections. Thus development of effective novel disinfectants could reduce the transmission of pathogens and decrease the risk of infection by antibiotic resistant organisms. The antimicrobial activity of amphiphiles, compounds with hydrophobic and hydrophilic regions, was first reported in 1935, and has influenced the synthesis of amphiphiles with variations in structure. In this study, three series of amphiphiles were synthesized by two subsequent Menshutkin reactions. Each amphiphile contains one or two hydrocarbon tails ranging from 8 ...


New 4-Aminoquinoline Compounds To Reverse Drug Resistance In P. Falciparum Malaria, And A Survey Of Early European Antimalarial Treatments, Katherine May Liebman 2014 Portland State University

New 4-Aminoquinoline Compounds To Reverse Drug Resistance In P. Falciparum Malaria, And A Survey Of Early European Antimalarial Treatments, Katherine May Liebman

Dissertations and Theses

Intermittent fevers caused by Plasmodium parasites have been known for millennia, and have caused untold human suffering. Today, millions of people are afflicted by malaria each year, and hundreds of thousands die. Historically, the most successful synthetic antimalarial drug was chloroquine, as it was safe, inexpensive, and highly efficacious. However, plasmodial resistance to chloroquine now greatly limits its utility. Previously in our laboratories it has been shown that attachment of a "reversal agent moiety" to the side chain of chloroquine can result in the restoration of activity against chloroquine-resistant strains of P. falciparum malaria. In the first part of the ...


Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan 2014 Western Kentucky University

Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan

Honors College Capstone Experience/Thesis Projects

We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with ...


Probing The Unfolding And The Stability Of The Last Four Metal Binding Domains Of Wilson Disease Protein Using Circular Dichroism And Novel Spectroscopic Techniques, Ibtesam Yaseen Alja’afreh 2014 Western Michigan University

Probing The Unfolding And The Stability Of The Last Four Metal Binding Domains Of Wilson Disease Protein Using Circular Dichroism And Novel Spectroscopic Techniques, Ibtesam Yaseen Alja’Afreh

Dissertations

Wilson disease protein is a copper-transporting P1B type ATPase. It has large N-terminal copper binding domain which is composed of six homologous sub-domains. Each of these six domains is ~72 residues and connected to one another by linking regions of various lengths. They all possess similar ferrodoxin fold, and metal-binding motif, MXCXXC.

The need of having six metal binding domains and the manner in which they are communicating with each other is not well understood. To better understand how the last four metal binding domains function, I pursued a detailed biophysical characterization of these domains. Using molecular biology I ...


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