A5063642190- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Origins and Evolution of Life
- RNA Interference and Gene Delivery
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- Bacterial Genetics and Biotechnology
- Cytomegalovirus and herpesvirus research
University of California, Irvine
2016-2023
Arizona State University
2016
In vitro selection experiments carried out on artificial genetic polymers require robust and faithful methods for copying information back forth between DNA xeno-nucleic acids (XNA). Previously, we have shown that Kod-RI, an engineered polymerase developed to transcribe templates into threose nucleic acid (TNA), can function with high fidelity in the absence of manganese ions. However, transcriptional efficiency this enzyme diminishes greatly when individual are replaced libraries sequences,...
Chemical modifications are necessary to ensure the metabolic stability and efficacy of oligonucleotide-based therapeutics. Here, we describe analyses α-(l)-threofuranosyl nucleic acid (TNA) modification, which has a shorter 3'-2' internucleotide linkage than natural DNA RNA, in context small interfering RNAs (siRNAs). The TNA modification enhanced nuclease resistance more 2'-O-methyl or 2'-fluoro ribose modifications. TNA-containing siRNAs were prepared as triantennary N-acetylgalactosamine...
Recent advances in polymerase engineering have made it possible to copy information back and forth between DNA artificial genetic polymers composed of TNA (α-l-threofuranosyl-(3′,2′) nucleic acid). This property, coupled with enhanced nuclease stability relative natural RNA, warrants further investigation into the structural functional properties as an polymer for synthetic biology. Here, we report a highly optimized chemical synthesis protocol constructing multigram quantities nucleosides...
Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution, studied in the context RNA chemical etiology. It has a four-carbon threose backbone place five-carbon ribose natural acids, yet forms stable antiparallel complementary Watson-Crick homoduplexes heteroduplexes with DNA RNA. TNA base-pairs more favorably than but reason unknown. Here, we employed NMR, ITC, UV, CD to probe structural dynamic properties RNA/TNA DNA/TNA. The results indicate that...
Natural and modified nucleoside triphosphates impact nearly every major aspect of healthcare research from DNA sequencing to drug discovery. However, a scalable synthetic route these molecules has long been hindered by the need for purification high performance liquid chromatography (HPLC). Here, we describe fundamentally different approach that uses novel P(V) pyrene pyrophosphate reagent generate derivatives are purified silica gel converted desired compounds on scales vastly exceeding...
Ligases are a class of enzymes that catalyze the formation phosphodiester bonds between an oligonucleotide donor with 5′ terminal phosphate and acceptor 3′ hydroxyl group. Here, we wished to explore substrate specificity naturally occurring DNA RNA ligases determine whether molecular recognition these is sufficiently general synthesize alternative genetic polymers backbone structures distinct from those found in nature. We chose threose nucleic acid (TNA) as model system, TNA known be...
An RNA-dependent RNA polymerase ribozyme that was highly optimized through in vitro evolution for the ability to copy a broad range of template sequences exhibits promiscuity toward other nucleic acids and acid analogues, including DNA, threose (TNA), arabinose (ANA). By operating on various templates, catalyzes multiple successive additions TNA, or ANA monomers, although with reduced efficiency compared monomers. The can also DNA TNA templates complementary RNAs, lesser extent it operate...
α-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer composed of vicinal 2′,3′-phosphodiester bonds linking adjacent threofuranosyl nucleosides. TNA one a small number polymers that are both highly resistant to nuclease digestion and capable cross-pairing with DNA RNA. Although efficient method for synthesizing nucleosides has been reported, very few advances have made in the synthesis phosphorylated compounds. Here, we describe α-l-threofuranosyl nucleoside...
The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the noncanonical nucleotides including threo-nucleotide building blocks TNA. Here, we examine ability activated threo-nucleotides participate in nonenzymatic template-directed polymerization. We find that primer extension multiple sequential monomers strongly disfavored relative ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest this due part slow formation imidazolium-bridged TNA dinucleotide...
Abstract G‐rich sequences can adopt four‐stranded helical structures, called G‐quadruplexes, that self‐assemble around monovalent cations like sodium (Na + ) and potassium (K ). Whether similar structures be formed from xeno‐nucleic acid (XNA) polymers with a shorter backbone repeat unit is an unanswered question significant implications on the fold space of functional XNA polymers. Here, we examine potential for TNA (α‐ l ‐threofuranosyl nucleic acid) to structure based planar G‐quartet...
α-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer in which the natural five-carbon ribose sugar found RNA has been replaced with unnatural four-carbon threose sugar. Despite a different sugar–phosphate backbone, TNA capable of forming stable, antiparallel Watson–Crick duplex structures itself and complementary strands DNA RNA. This property intersystem base pairing, coupled chemical simplicity relative to ribose, provides support for as candidate progenitor evolution...
ABSTRACT The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the noncanonical nucleotides including threo-nucleotide building blocks TNA. Here we examine ability activated threo-nucleotides participate in nonenzymatic template-directed polymerization. We find that primer extension multiple sequential monomers strongly disfavored relative ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest this due part slow formation imidazolium-bridged TNA...