Sequence and secondary structural analysis of a novel class of RNA aptamers that inhibit reverse transcriptase

2012 ◽  
Author(s):  
◽  
Angela Whatley
Keyword(s):  
Reverse Transcriptase ◽  
Rna Aptamers ◽  
University Of Missouri ◽  
Hiv Rna ◽  
Cellular Assays ◽  
Subtype B ◽  
Single Target ◽  
Ic50 Values ◽  
The University ◽  
Major Target

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] RNA aptamers are synthetic RNAs selected for their ability to bind a molecular target. Reverse Transcriptase (RT) is the major target of antiretroviral therapy used in the treatment of HIV. RNA aptamers were selected to bind to RT of HIV-1 subtype B. Previous work showed aptamers from this selection inhibited various RT enzymatic activities, and have also been shown to inhibit viral replication in cellular assays. Most of the aptamers from this selection have predicted pseudoknot structures. The aptamers were classified into Pseudoknot families. Family 1 Pseudoknots (F1Pk) have a conserved UCCG sequence in stem one. Family 2 Pseudoknots (F2Pk) aptamers have CYGG (Y is pyrimidine either C or U). Aptamer secondary structural families are correlated with inhibitory behavior. F2Pk aptamers inhibit a broader range of RT subtypes compared to F1Pk. In the present work we present results of a screen into the inhibitory behavior of a novel family of anti RT aptamer from a previously well- studied pool. We found a group of aptamers that inhibit RT from subtype B very well and have novel secondary structure. These aptamers fold into stem loops with a highly conserved UCAA bulge. Aptamers in the UCAA family inhibit RT very well in primer extension assays and have IC50 values as low as 1.6nM. This work highlights the diversity of RNA secondary structures that are able to bind to a single target.

Aptamers against viral proteins as a tool to answer biological questions

2019 ◽  
Author(s):  
◽  
Carolina Camargo
Keyword(s):  
Lentiviral Vector ◽  
Rna Aptamers ◽  
Target Cells ◽  
University Of Missouri ◽  
Practical Applications ◽  
Intracellular Expression ◽  
The University ◽  
Further Development ◽  
Viral Surface

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] There are two experimental chapters in this dissertation in which the fundamental questions center around aptamers and viruses and how these two concepts interlace. The first experimental chapter (chapter two) seeks to utilize previously characterized aptamers against HIV-1 Reverse Transcriptase (RT) that will be delivered by a lentiviral vector and which intracellular expression from different human promoters was evaluated. The goal of this study was to identify important elements of vector design that will impact transgene expression in target cells. This study was based on the hypothesis that intracellular expression of RNA aptamers delivered by a lentiviral vector could offer a platform to enable adequate aptamer expression that would translate into viral suppression. And the second experimental chapter (chapter four) describes an in vitro 2'FY-RNA selection against Filoviral glycoproteins and outlines three different strategies that were followed to achieve selection of specific aptamers. Aptamers described in this chapter were able to recognize Ebolavirus glycoprotein ectodomain as well as in its native conformation displayed on the viral surface. Taking the observations obtained in this dissertation, aptamer technology could be expanded into further development for practical applications.

Advances in aptamer evolution and engineering

2016 ◽  
Author(s):  
◽  
Khalid Kamal Alam
Keyword(s):  
High Throughput Sequencing ◽  
Target Selection ◽  
Three Dimensional ◽  
Rna Aptamers ◽  
Hiv Reverse Transcriptase ◽  
University Of Missouri ◽  
Selection Approach ◽  
And Function ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Aptamers are single-stranded nucleic acids that fold into unique three-dimensional shapes that allow them to bind with high affinity and specificity to targets of interest. They are selected through the process of in vitro evolution, wherein large libraries of randomized sequence are iteratively partitioned and amplified to enrich for high-fitness, functional molecules. Selected libraries are sequenced and individual aptamers are characterized for their structure and function. Aptamers have found use as research tools, diagnostics, and therapeutics and in the control of biological systems. The work described herein presents several advancements to the selection and application of aptamers. I first describe an aptamer bioinformatics platform, FASTAptamer, which performs the primary sequence tasks common to all combinatorial selection techniques. I then describe a poly-target selection approach that leverages high-throughput sequencing, the aptamer bioinformatics platform, and parallel selections against a family of related targets to identify the first RNA aptamers capable of potent broad-spectrum inhibition of HIV reverse transcriptase. Finally, this work describes the engineering and in vitro validation of a bifurcated aptamer, Split-Broccoli, for direct visualization of RNA:RNA processes.

TEM study of boron additions to cobalt aluminide

1988 ◽  
Vol 46 ◽  
pp. 546-547
Author(s):  
Gerald B. Feldewerth
Keyword(s):  
High Temperature ◽  
Turbine Engines ◽  
Major Drawback ◽  
University Of Missouri ◽  
Specific Strength ◽  
Aerospace Applications ◽  
Wide Range ◽  
Ordered Alloys ◽  
The University ◽  
Very High

In recent years an increasing emphasis has been placed on the study of high temperature intermetallic compounds for possible aerospace applications. One group of interest is the B2 aiuminides. This group of intermetaliics has a very high melting temperature, good high temperature, and excellent specific strength. These qualities make it a candidate for applications such as turbine engines. The B2 aiuminides exist over a wide range of compositions and also have a large solubility for third element substitutional additions, which may allow alloying additions to overcome their major drawback, their brittle nature.One B2 aluminide currently being studied is cobalt aluminide. Optical microscopy of CoAl alloys produced at the University of Missouri-Rolla showed a dramatic decrease in the grain size which affects the yield strength and flow stress of long range ordered alloys, and a change in the grain shape with the addition of 0.5 % boron.

MARS — Its Tenth Anniversary of Operation and its Future

1980 ◽  
Vol 19 (03) ◽  
pp. 125-132
Author(s):  
G. S. Lodwick ◽  
C. R. Wickizer ◽  
E. Dickhaus
Keyword(s):  
Conceptual Development ◽  
Administrative Support ◽  
Final Section ◽  
Economic Benefits ◽  
Hospital Environment ◽  
Computer Scientist ◽  
University Of Missouri ◽  
Complete Bibliography ◽  
The University ◽  
Economic Considerations

The Missouri Automated Radiology System recently passed its tenth year of clinical operation at the University of Missouri. This article presents the views of a radiologist who has been instrumental in the conceptual development and administrative support of MARS for most of this period, an economist who evaluated MARS from 1972 to 1974 as part of her doctoral dissertation, and a computer scientist who has worked for two years in the development of a Standard MUMPS version of MARS. The first section provides a historical perspective. The second deals with economic considerations of the present MARS system, and suggests those improvements which offer the greatest economic benefits. The final section discusses the new approaches employed in the latest version of MARS, as well as areas for further application in the overall radiology and hospital environment. A complete bibliography on MARS is provided for further reading.

New Efavirenz Derivatives and 1,2,3-Triazolyl-phosphonates as Inhibitors of Reverse Transcriptase of HIV-1

2018 ◽  
Vol 18 (17) ◽  
pp. 1494-1505 ◽  
Author(s):  
Carolina C.P. Costa ◽  
Nubia Boechat ◽  
Monica M. Bastos ◽  
Fernando de C. da Silva ◽  
Andressa Marttorelli ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Triazole Ring ◽  
Biological Evaluation ◽  
World Health ◽  
Hiv Reverse Transcriptase ◽  
Ic50 Values ◽  
Health Organization ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
New Compounds

Background: According to the World Health Organization (WHO), the fight against Acquired Immunodeficiency Syndrome (AIDS) is still one of the most significant challenges facing humanity. Worldwide, it is estimated that 36.7 million people are infected by the Human Immunodeficiency Virus (HIV). Despite the variety of available drugs, the search for new enzymatic inhibitors of HIV is still important due to the presence of adverse effects and the development of resistant strains. Therefore, the present study aimed to design, synthesize, and biologically evaluate novel inhibitors of HIV Reverse Transcriptase (RT). Materials and Methods: These compounds were obtained in two series, and compounds in both series contain a 1,2,3-triazole ring in their structures. The compounds in the first series are Efavirenz (EFV) analogues with the N-1 position substituted by another important fragment as described in the medicinal chemistry literature on anti-HIV drugs. The second series has a phosphonate chain similar to that in the structure of Tenofovir Disoproxil Fumarate (TDF). Results and Conclusion: The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations (the concentration needed to reduce the enzymatic activity by 50%, IC50 values, 0.8-1.9 µM). Among the compounds in the first series, the three with the lowest IC50 values had values between 0.8-0.9 µM, and of those in the second series, the most potent had an IC50 value of 1.1 µM; compounds in both series were equipotent to TDF (1.2 µM). Thus, the new compounds could be considered lead compounds for the development of new antiretroviral compounds.

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Phylogenetic Analyses ◽  
Resistance Mutations ◽  
Protease Inhibition ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

An Interactive Morphological Matrix Computational Design Tool: A Hybrid of Two Methods

2007 ◽  
Author(s):  
Cari R. Bryant ◽  
Matt Bohm ◽  
Robert B. Stone ◽  
Daniel A. McAdams
Keyword(s):  
Computational Design ◽  
Design Tool ◽  
Design Tools ◽  
Concept Generation ◽  
University Of Missouri ◽  
Generation Algorithm ◽  
Design Theories ◽  
The University ◽  
Matrix Generator

This paper builds on previous concept generation techniques explored at the University of Missouri - Rolla and presents an interactive concept generation tool aimed specifically at the early concept generation phase of the design process. Research into automated concept generation design theories led to the creation of two distinct design tools: an automated morphological search that presents a designer with a static matrix of solutions that solve the desired input functionality and a computational concept generation algorithm that presents a designer with a static list of compatible component chains that solve the desired input functionality. The merger of both the automated morphological matrix and concept generation algorithm yields an interactive concept generator that allows the user to select specific solution components while receiving instantaneous feedback on component compatibility. The research presented evaluates the conceptual results from the hybrid morphological matrix approach and compares interactively constructed solutions to those returned by the non-interactive automated morphological matrix generator using a dog food sample packet counter as a case study.

Beyond the border war : student civil rights activism at the University of Kansas and the University of Missouri, 1946-1954

2020 ◽  
Author(s):  
◽  
Mary Beth Brown
Keyword(s):  
World War Ii ◽  
Civil Rights ◽  
Race Relations ◽  
Student Activism ◽  
University Of Kansas ◽  
University Of Missouri ◽  
Effect Change ◽  
Student Activists ◽  
The University ◽  
The 19Th Century

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA AT REQUEST OF AUTHOR.] This dissertation examines post-World War II student civil rights activism at two Midwestern college campuses, the University of Missouri (MU) and the University of Kansas (KU). Missouri and Kansas have conflicting histories concerning race dating back to Bleeding Kansas and the history of race relations on the campuses of KU and MU. This history is especially complicated during the period between 1946 and 1954 because of heightened student activism that challenged racial injustices. Race relations on campus largely mirrored that of the state's political environment, with KU having integrated in the 19th century, whereas MU did not desegregate until 1950. However, the same did not apply to the success of student activists at each school where MU students found success fighting against discriminatory practices in Columbia, whereas local business leaders and the university administration stymied KU students. The dissertation examines the exchange of ideas and strategy among students, which occurred through athletics, debates, guest speakers, and various regional and national groups. In particular, the study argues that campus spaces, such as residential co-ops and student organizations, were deeply significant because they served as incubators of activism by offering students a place to talk about racial and social injustice and plan ways to challenge these inequalities and effect change on campus and in the broader community.

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