Base Sequence In Nucleic Acids Research Articles

Transient Out‐of‐Equilibrium Nucleic Acid‐Based Dissipative Networks and Their Applications

AbstractDynamic, dissipative reactions play important roles in biological processes, and emulating such biological processes by artificial circuits and networks is a challenging topic in the area of Systems Chemistry. The present article summarizes efforts to apply the information encoded in the base sequence of nucleic acids to assemble transient, dissipative DNA‐based networks mimicking natural processes. The design principles of the transient nucleic acid‐based systems are introduced. Triggered reaction moduli lead to a transient intermediary constituent recovered to the parent moduli by enzymes, DNAzyme, or light as control units are described. Transient DNA‐based circuitries of enhanced complexities revealing temporal gated or cascaded transformations are demonstrated. Different applications of dynamically triggered transient circuits are introduced, including the temporal aggregation and deaggregation of plasmonic nanoparticles or semiconductor quantum dots and the control over their optical properties, the transient release and uptake of loads by aptamer scaffolds, and the transient reconfiguration of constitutional dynamic networks and the control over emergent catalytic functions. The future perspectives of dissipative nucleic acid‐based networks and their potential future applications are discussed.

Biochemistry beyond the lab

I love this issue for the diversity of the articles within it. Biochemistry knowledge has impacted on global health and nutrition and is also supporting new approaches to slow climate change. This issue covers the past and the present and looks to the future for biochemistry. It could have been a very large issue!The UK has around 90,000 people employed as biochemists across industry, academia and healthcare. They work in areas such as forensic science, health and agriculture. Earlier this year our issues have focused on the significant contributions biochemistry has given to the COVID- 19 pandemic, and there is a new article on that topic in this issue. More surprising might be the biochemistry of bacteria that support the generation of electricity or the removal of plastic pollution.Biochemistry emerged as a field of academic study in the very early 20th century. The first chair of biochemistry in the UK (at the University of Liverpool), Benjamin Moore was also responsible for founding the Biochemical Journal in 1906 and was a founder of the Biochemical Society in 1911. I felt, for this issue, it’s worth a look back at the establishment of biochemistry as a field of biology back in the early 1900s.Biochemistry has had an extremely busy century, uncovering the processes and proteins within living organisms. I have to mention the work of Frederick Sanger who won the Nobel Prize in chemistry twice, the first for his work on determining the chemical structure, the amino acid sequence, of insulin in 1958 and then for his work on determining the base sequence of nucleic acids in 1980. The 100th anniversary of insulin was celebrated by a special issue of The Biochemist earlier in 2021. Dorothy Hodgkin went on to determine the structure of insulin through X-ray chromatography. Of course, these firsts and the development of the methods led to the discovery of many other protein structures, an important step in visualizing the minutiae of life – another theme we gave an issue to earlier this year.Studying, working in or researching biochemistry opens up a new, very small world where your knowledge gives you privileged access. Each issue I edit teaches me more about new advances in this field, which moves forward at a rapid pace, as methods for biochemistry evolve and technology becomes more powerful, allowing us to see and understand more about the molecular level. So, whether you are a student of biochemistry, a seasoned biochemist, a former biochemist or just have an interest in this fascinating area you will definitely find something new in this issue.

History of Research on Antisense Oligonucleotide Analogs

In the search for novel therapeutics, antisense oligonucleotide (ASO) analogs have been a major focus of research for over 40 years. They use the antisense strategy, namely they have a nucleic acid base sequence that is complementary to a portion of a specific mRNA that is produced in the cell, or to a viral RNA, in order to selectively inhibit gene expression. Oligonucleotides need to be chemically modified to stabilize them against hydrolysis by endogenous nucleases. Until now several phosphorothioate (PS) oligonucleotide analogs have been approved by the FDA for human use. This article seeks to provide a history of this subject to date.

Interplay between Short-Range Attraction and Long-Range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes.

In eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a windowlike phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using ribonucleoprotein-inspired polypeptides with low-complexity RNA-binding sequences as well as an archetypal disordered RNP, fused in sarcoma, as model systems, we investigate the molecular driving forces underlying this nonmonotonous phase transition. We show that an interplay between short-range cation-π attractions and long-range electrostatic forces governs the heterotypic RLC behavior of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, control the two-phase coexistence regime, regulate material properties of polypeptide-RNA condensates, and oppose condensate reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloidlike cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.

5-Amidodansyl-U (UD) Peptide Nucleic Acid (PNA) as a Fluorescent Sensor of the Local Dielectric Constant (ε) in PNA Duplexes: Major Grooves in PNA Duplexes Are More Hydrophobic Than Major Grooves in DNA–DNA Duplexes

Peptide nucleic acids (PNA) show great promise for the development of antisense drugs owing to their superior binding property with complementary DNA/RNA. They recognize complementary DNA/RNA/PNA via hydrogen bonding and electrostatic interaction whose strengths depend on their chemical environment. It is therefore important to understand the effects of local dielectrics in the major/minor grooves of PNA:DNA/RNA/PNA duplexes that influence its superior binding. By employing 5-amidodansyl U on PNA as a fluoroprobe of the local environment and measuring the polarity-sensitive Stokes shift, it is demonstrated that compared to the major groove of DNA–DNA duplexes, the analogous major groove of PNA:DNA/RNA/PNA duplexes is more hydrophobic (lower ε), and sequence-dependent polarity changes are seen in all PNA duplexes. The results highlight the effects of chemical modifications of backbone and base sequence in nucleic acids on the local environment of grooves, leading to a dielectric continuum that may have implications for the binding of ligands and macromolecules in grooves of nucleic acid duplexes.

Stimuli-Responsive DNA-Based Hydrogels: From Basic Principles to Applications.

The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution ↔ hydrogel ↔ solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.

DNA switches: from principles to applications.

The base sequence of nucleic acid encodes structural and functional properties into the biopolymer. Structural information includes the formation of duplexes, G-quadruplexes, i-motif, and cooperatively stabilized assemblies. Functional information encoded in the base sequence involves the strand-displacement process, the recognition properties by aptamers, and the catalytic functions of DNAzymes. This Review addresses the implementation of the information encoded in nucleic acids to develop DNA switches. A DNA switch is a supramolecular nucleic acid assembly that undergoes cyclic, switchable, transitions between two distinct states in the presence of appropriate triggers and counter triggers, such as pH value, metal ions/ligands, photonic and electrical stimuli. Applications of switchable DNA systems to tailor switchable DNA hydrogels, for the controlled drug-release and for the activation of switchable enzyme cascades, are described, and future perspectives of the systems are addressed.

Organizing protein–DNA hybrids as nanostructures with programmed functionalities

The structural and functional information encoded in the base sequence of nucleic acids provides a means to organize hybrid protein-DNA nanostructures with pre-designed, programmed functionality. This review discusses the activation of enzyme cascades in supramolecular DNA-protein hybrid structures, the bioelectrocatalytic activation of redox enzymes on DNA scaffolds, and the programmed positioning of enzymes on 1D, 2D and 3D DNA nanostructures. These systems provide starting points towards the design of interconnected enzyme networks. Substantial progress in the tailoring of functional protein-DNA nanostructures has been accomplished in recent years, and advances in this field warrant a comprehensive discussion. The application of these systems for the control of biocatalytic transformations, for amplified biosensing, and for the synthesis of metallic nanostructures are addressed, and future prospects for these systems are highlighted.

Nucleic acid drugs: a novel approach

Nucleic acid base sequence of proteins plays a crucial role in the expression of gene. The gene is responsible for the synthesis of proteins and these proteins, which are synthesized, are responsible for the biological process and also for dreadful diseases as well. Once if the nucleic acid sequence is altered, we would be able to block or transfer the message for protein synthesis, there by preventing the particular protein, which is responsible for the disease. These nucleic acids act as drugs by different mechanisms, they may bind with the synthesized proteins, and they can hybridize to a messenger RNA leading to translation arrest or may induce degradation to target RNA. In this way the nucleic acids act as drug for inhibiting gene expression or protein synthesis. This article examines about the different types of nucleic acid drugs, their mechanisms, advantages, drawbacks and their future prospects. Key Words: Aptamers, ribozymes, antisense oligonucleotides. African Journal of Biotechnology Vol.3(12) 2004: 662-666

Paul Berg—American Nobel Laureate

American biochemist and molecular biologist Paul Berg received the 1980 Nobel Prize in chemistry for “his fundamental studies of the biochemistry of nucleic acids, with particular regard for recombinant DNA.” In addition, he developed the new technology of genetic engineering. Berg shared the Nobel Prize with American chemist Walter Gilbert (1932-) and English chemist Frederick Sanger (1918-). Gilbert determined the sequence of bases in DNA by a method applicable to single- and double-stranded DNA, and Sanger determined the base sequence of nucleic acid. Sanger had previously won the 1958 Nobel Prize in chemistry for his work on the structure of proteins, especially insulin. Berg was born on June 30, 1926, in New York City. He received his secondary education at Abraham Lincoln High School and graduated in 1943. He entered Pennsylvania State University in University Park, but his education was interrupted for service in the US Navy from 1944 to 1946. After his discharge from the navy, he returned to Pennsylvania State University and graduated with a BS degree in biochemistry in 1948. Berg was a graduate student at Western Reserve University (now Case Western Reserve) in Cleveland, Ohio, and received a PhD degree in 1952. Berg spent 2 years (1952-1953) as a postdoctoral fellow at the Institute of Cytophysiology in Copenhagen, Denmark. After he returned from Denmark, he worked for 1 year with 1959 Nobel laureate Arthur Kornberg (1918-) at Washington University in St Louis, Mo. While working with Kornberg, Berg became familiar with the chemistry of DNA and RNA. He became an assistant professor of microbiology and remained at Washington University until 1959. In 1959, Berg left St Louis to become an associate professor at Stanford University in Stanford, Calif. In 1969, he was named chair of the biochemistry department. While at Stanford University, Berg became interested in the role of transfer RNA (tRNA), a substance that delivers amino acids to the proper position during protein assembly. Berg elucidated the role of tRNA in protein assembly by purifying many of the different tRNAs and the enzymes that link them to the correct amino acids. Berg took a sabbatical leave to work at the Salk Institute (La Jolla, Calif) with Italian virologist Renata Dulbecco (1914-), another Nobel laureate (1975 prize in physiology or medicine). His aim was to determine whether a method could be devised to examine and manipulate the complicated genes of multicellular organisms, including those of the human body. In 1968, Berg returned to Stanford University to begin his research on the genes of a monkey tumor virus. He began his first experiments on recombinant DNA about 1970. During the course of studying the action of isolated genes, he developed methods for splitting DNA molecules at selected sites and attaching segments of the molecules to the DNA of a virus or plasmid, which could enter bacterial or animal cells. The foreign DNA was incorporated with the host and caused the synthesis of proteins not ordinarily found there. The techniques that Berg and his colleagues developed enabled researchers not only to manipulate genes to create new pharmaceuticals, such as interferon and growth hormones, but also to study the molecular biology of more complicated organisms in detail. Berg has received many honors and awards in addition to the Nobel Prize. He was honored on a stamp issued by the Pacific islands of Palau in 2000.

What would T. H. Huxley have made of prion diseases?

T. H. Huxley was "Darwin's bulldog," and took the offensive in championing the cause of evolution against skeptical scientists and outraged theologians. As such, he took part in one of the great "paradigm shifts" of biology, at the end of the nineteenth century. Huxley was a rigorous scientist and wrote important articles on scientific method, as well as publishing extensively on a wide range of subjects in natural history. In the second half of the twentieth century, the "prion hypothesis" was put forward to explain the pathogenesis of a curious group of diseases known as the transmissible spongiform encephalopathies. This also involved a "paradigm shift" because the prion hypothesis postulated that biologically relevant information could be enciphered in protein conformation (rather than encoded in nucleic acid base sequences), and could be transmitted from one molecule to another, thereby causing infectious disease. This article examines a few of Huxley's remarks to speculate on how he might have responded to the scientific debate about prion disease had he lived a century later.

Detection of the ΔF508 mutation in the CFTR gene by means of time-resolved fluorescence methods

A rapid recognition in the base sequence of nucleic acids is an important prerequisite toward the diagnosis of genetic diseases and their carrier states. We have developed a hybridisation method in which a fluorescently labeled oligonucleotide is used to detect point mutations in a target by a simple fluorescence lifetime analysis of the emission of the fluorescent label. We applied this method to detect the ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a model system and with biologically derived PCR product and discuss the potential generality of this method.

Recognition of Point Mutations in Dna By Means of Time Resolved Fluorescence Methods

A rapid recognition of aberrations in the base sequence of nucleic acids is an important step toward the diagnosis of genetic diseases. We have developed a hybridization method in which a fluorescently labeled oligonucleotide is used to detect point mutations in a target by a simple fluorescence lifetime analysis of the emission of the fluorescent label.

4982326 Method for analyzing autoradiograph for determining base sequence of nucleic acid: Takash Kaneko, Hadano, Japan assigned to Fuji Photo Film Co Ltd

4982326 Method for analyzing autoradiograph for determining base sequence of nucleic acid: Takash Kaneko, Hadano, Japan assigned to Fuji Photo Film Co Ltd

4972325 Signal processing method for determining base sequence of nucleic acid: Makoto Hara, Minami ashigara, Japan assigned to Fuji Photo Film Co Ltd

4972325 Signal processing method for determining base sequence of nucleic acid: Makoto Hara, Minami ashigara, Japan assigned to Fuji Photo Film Co Ltd

4982326 Method for analyzing autoradiograph for determining base sequence of nucleic acid: Takash Kaneko, Hadano, Japan assigned to Fuji Photo Film Co Ltd

4982326 Method for analyzing autoradiograph for determining base sequence of nucleic acid: Takash Kaneko, Hadano, Japan assigned to Fuji Photo Film Co Ltd

4958281 Signal processing method for determining base sequence of nucleic acid: Makot Hara, Kanagawa, Japan assigned to Fuji Photo Film Co Ltd

4958281 Signal processing method for determining base sequence of nucleic acid: Makot Hara, Kanagawa, Japan assigned to Fuji Photo Film Co Ltd

4885696 Signal processing method for determining base sequence of nucleic acid: Makoto Hara, Minami ashigari, Japan assigned to Fuji Photo Film Co Ltd

4885696 Signal processing method for determining base sequence of nucleic acid: Makoto Hara, Minami ashigari, Japan assigned to Fuji Photo Film Co Ltd

4802101 Signal processing method for determining base sequence of nucleic acid: Makot Hara, Kaisei, Japan assigned to Fuji Photo Film Co Ltd

4802101 Signal processing method for determining base sequence of nucleic acid: Makot Hara, Kaisei, Japan assigned to Fuji Photo Film Co Ltd

Reactive oligonucleotide derivatives and sequence-specific modification of nucleic acids

Selective modification of nucleic acid base sequences can be achieved by complementary oligonucleotides carrying reactive groups. Different types of reactive groups are briefly presented.