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Articles 1 - 8 of 8
Full-Text Articles in Biotechnology
Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck
Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck
Theses and Dissertations--Pharmacy
In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.
The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABAA receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABAA receptor interaction suggests that …
Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani
Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani
Theses and Dissertations--Pharmacy
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.
The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …
Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber
Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber
Theses and Dissertations--Pharmacy
Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …
Biosynthetic Mechanism Of The Antibiotic Capuramycin, Erfu Yan
Biosynthetic Mechanism Of The Antibiotic Capuramycin, Erfu Yan
Theses and Dissertations--Pharmacy
A-102395 is a member of the capuramycin family of antibiotics which was isolated from the culture broth of Amycolatopsis sp. SANK 60206. A-102339 is structurally classified as a nucleoside antibiotic, which like all members of the capuramycin family, inhibits bacterial MraY (translocase I) with IC50 of 11 nM which is the lowest among the capuramycin family. A semisynthetic derivative of capuramycin is currently in clinical trials as an antituberculosis antibiotic, suggesting high potential for using A-102395 as a starting point for new antibiotic discovery. In contrast to other capuramycins, A-102395 has a unique arylamine-containing polyamide side chain. The biosynthetic …
Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi
Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi
Theses and Dissertations--Pharmacy
The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies.
One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting …
Towards Elucidation Of The Mechanism Of Biological Nanomotors, Zhengyi Zhao
Towards Elucidation Of The Mechanism Of Biological Nanomotors, Zhengyi Zhao
Theses and Dissertations--Pharmacy
Biological functions such as cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging, and cell entry all involve biomotor-driven DNA translocation. In the past, the ubiquitous biological nanomotors were classified into two categories: linear and rotation motors. In 2013, we discovered a third type of biomotor, revolving motor without rotation. The revolving motion is further found to be widespread among many biological systems. In addition, the detailed sequential action mechanism of the ATPase ring in the phi29 dsDNA packaging motor has been elucidated: ATP binding induces a conformational entropy alternation of ATPase …
Development Of New Biological Nanopores And Their Application For Biosensing And Disease Detection, Shaoying Wang
Development Of New Biological Nanopores And Their Application For Biosensing And Disease Detection, Shaoying Wang
Theses and Dissertations--Pharmacy
Nanopore technology has recently emerged as a new real-time single molecule sensing method. The current dominant technologies, such as mass spectrometry and immunoassay, for protein analysis is still slow and complex, which can’t meet the urgent need and fields of use. Development of a highly simple, portable and sensitive detection system for pathogen detection, disease diagnosis, and environmental monitoring is in great need. Membrane embedded Phi29 connector nanopore, the first protein nanopore coming from bacteriophage, was mainly focusing on DNA and RNA translocation in previous studies. Here, Phi29 connector nanopore was first time established for antibody detection by engineering Epithelial …
Towards Elucidation Of A Viral Dna Packaging Motor, Chad T. Schwartz
Towards Elucidation Of A Viral Dna Packaging Motor, Chad T. Schwartz
Theses and Dissertations--Pharmacy
Previously, gp16, the ATPase protein of phi29 DNA packaging motor, was an enigma due to its tendency to form multiple oligomeric states. Recently we employed new methodologies to decipher both its stoichiometry and also the mechanism in which the protein functions to hydrolyze ATP and provide the driving force for DNA packaging. The oligomeric states were determined by biochemical and biophysical approaches. Contrary to many reported intriguing models of viral DNA packaging, it was found that phi29 DNA packaging motor permits the translocation of DNA unidirectionally and driven cooperatively by three rings of defined shape. The mechanism for the generation …