scholarly journals Advances on Aptamers against Protozoan Parasites

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 584 ◽  
Author(s):  
Juan Ospina-Villa ◽  
César López-Camarillo ◽  
Carlos Castañón-Sánchez ◽  
Jacqueline Soto-Sánchez ◽  
Esther Ramírez-Moreno ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Drug Carriers ◽  
Rna Aptamers ◽  
Health Concern ◽  
Dimensional Structure ◽  
Parasitic Infections ◽  
Attractive Alternative ◽  
Protozoan Parasites ◽  
Rna Sequences ◽  
Dna And Rna

Aptamers are single-stranded DNA or RNA sequences with a unique three-dimensional structure that allows them to recognize a particular target with high affinity. Although their specific recognition activity could make them similar to monoclonal antibodies, their ability to bind to a large range of non-immunogenic targets greatly expands their potential as tools for diagnosis, therapeutic agents, detection of food risks, biosensors, detection of toxins, drug carriers, and nanoparticle markers, among others. One aptamer named Pegaptanib is currently used for treating macular degeneration associated with age, and many other aptamers are in different clinical stages of development of evaluation for various human diseases. In the area of parasitology, research on aptamers has been growing rapidly in the past few years. Here we describe the development of aptamers raised against the main protozoan parasites that affect hundreds of millions of people in underdeveloped and developing countries, remaining a major health concern worldwide, i.e. Trypanosoma spp., Plasmodium spp., Leishmania spp., Entamoeba histolytica, and Cryptosporidium parvuum. The latest progress made in this area confirmed that DNA and RNA aptamers represent attractive alternative molecules in the search for new tools to detect and treat these parasitic infections that affect human health worldwide.

Analysis of recombinant tagged equilibrative nucleoside transporter 1 (ENT1) expressed in E. coliThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 246-255 ◽  
Author(s):  
German Reyes ◽  
Nicole M.I. Nivillac ◽  
Maria Chalsev ◽  
Imogen R. Coe
Keyword(s):  
Membrane Proteins ◽  
Large Scale ◽  
Peer Review Process ◽  
Three Dimensional ◽  
Drug Uptake ◽  
Dimensional Structure ◽  
Parasitic Infections ◽  
Scale Production ◽  
Nucleoside Transporter ◽  
Intracellular Loop

Nucleoside transporters (NTs) are integral membrane proteins necessary for the cellular entry of nucleoside analog drugs used in chemotherapeutic treatment of conditions such as cancer and viral or parasitic infections. NTs are also the targets of certain drugs used in the treatment of various cardiovascular conditions. Because of the importance of NTs in drug uptake, determination of the three-dimensional structure of these proteins, particularly hENT1, has the potential to improve these treatments through structure-based design of more specifically targeted and transported drugs. In this paper, we use NMR spectroscopy to investigate the structure of the large intracellular loop between transmembrane domains 6 and 7 and we also describe a method for the successful overexpression of full-length hENT1 in a bacterial system. Recombinant tandem histidine-affinity (HAT) and 3×FLAG tagged hENT1 was overexpressed in E. coli, affinity purified, and functionally characterized by nitrobenzylthioinosine (NBTI) binding. Anti-3×FLAG immunodetection confirmed the expression of N-HAT-3×FLAG-hENT1, while increased NBTI binding (3.2-fold compared with controls) confirmed the conformational integrity of the recombinant hENT1 within the bacterial inner membrane. Yields of recombinant hENT1 using this approach were ∼15 µg/L of bacterial culture and this approach provides a basis for large-scale production of protein for a variety of purposes.

scholarly journals Aptamers and Cancer

2016 ◽  
Vol 1 (1) ◽  
pp. 3
Author(s):  
Nasrin Yazdanpanahi ◽  
Mehrdad Hashemi ◽  
Abolfazl Movafagh
Keyword(s):  
Nucleotide Sequence ◽  
High Efficiency ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Target Molecule ◽  
Dna And Rna ◽  
Specific Proteins

Oligonucleotides Aptamers are single strands of DNA and RNA with the length of 20-100 nucleotides or peptides and unique three dimensional structure that is affected by nucleotide sequence. The structure exclusively influences aptamers’ bindings with its target molecule. It reduces performance or inactivate protein and this feature is used for therapeutic purposes. In addition and through connecting to signature molecule, aptamers are used to detect specific proteins. High efficiency of aptamer technology makes them a valuable tool for diagnosing and treating different diseases including cancer. The present study is an attempt to review recent studies in this field.

scholarly journals Current Advances in the Development of Diagnostic Tests Based on Aptamers in Parasitology: A Systematic Review

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1046
Author(s):  
Juan David Ospina-Villa ◽  
Alondra Cisneros-Sarabia ◽  
Miryan Margot Sánchez-Jiménez ◽  
Laurence A. Marchat
Keyword(s):  
Systematic Review ◽  
Diagnostic Tests ◽  
Three Dimensional ◽  
High Specificity ◽  
Detection Methods ◽  
Attractive Alternative ◽  
Rna Sequences ◽  
Sensitivity And Selectivity ◽  
Meta Analyses

Aptamers are single-stranded DNA or RNA sequences of 20–80 nucleotides that interact with different targets such as: proteins, ions, viruses, or toxins, through non-covalent interactions and their unique three-dimensional conformation. They are obtained in vitro by the systematic evolution of ligands by exponential enrichment (SELEX). Because of their ability of target recognition with high specificity and affinity, aptamers are usually compared to antibodies. However, they present many advantages that make them promising molecules for the development of new methods for the diagnosis and treatment of human diseases. In medical parasitology, aptamers also represent an attractive alternative for the implementation of new parasite detection methods, easy to apply in endemic regions. The aim of this study was to describe the current advances in the development of diagnostic tests based on aptamers in parasitology. For this, articles were selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with specific inclusion and exclusion criteria. The 26 resulting articles deal with the use of aptamers for the detection of six important protozoa that affect human health. This systematic review clearly demonstrates the specificity, sensitivity and selectivity of aptamers and aptasensors, that certainly will soon become standard methods in medical parasitology.

scholarly journals The Application Status of Nanoscale Cellulose-Based Hydrogels in Tissue Engineering and Regenerative Biomedicine

2021 ◽  
Vol 9 ◽  
Author(s):  
Chenyang Wang ◽  
Jin Bai ◽  
Pei Tian ◽  
Rui Xie ◽  
Zifan Duan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Biomedical Applications ◽  
Cellulose Nanofibers ◽  
Three Dimensional ◽  
Drug Carriers ◽  
Wound Dressings ◽  
Skeletal Structure ◽  
Future Perspective ◽  
Dimensional Structure ◽  
Mechanical And Thermal Properties

As a renewable, biodegradable, and non-toxic material with moderate mechanical and thermal properties, nanocellulose-based hydrogels are receiving immense consideration for various biomedical applications. With the unique properties of excellent skeletal structure (hydrophilic functional groups) and micro-nano size (small size effect), nanocellulose can maintain the three-dimensional structure of the hydrogel to a large extent, providing mechanical strength while ensuring the moisture content. Owing to its unique features, nanocellulose-based hydrogels have made excellent progress in research and development on tissue engineering, drug carriers, wound dressings, development of synthetic organs, 3D printing, and biosensing. This review provides an overview of the synthesis of different types of nanocellulose, including cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, and describes their unique features. It further provides an updated knowledge of the development of nanocellulose-based functional biomaterials for various biomedical applications. Finally, it discusses the future perspective of nanocellulose-based research for its advanced biomedical applications.

scholarly journals Crystal structure of an RNA polymerase ribozyme in complex with an antibody fragment

2011 ◽  
Vol 366 (1580) ◽  
pp. 2918-2928 ◽  
Author(s):  
Joseph A. Piccirilli ◽  
Yelena Koldobskaya
Keyword(s):  
Metal Ion ◽  
Rna Binding ◽  
Rna World ◽  
Three Dimensional ◽  
Antibody Fragment ◽  
Single Step ◽  
Dimensional Structure ◽  
Rna Sequences ◽  
Rna Polymerization

All models of the RNA world era invoke the presence of ribozymes that can catalyse RNA polymerization. The class I ligase ribozyme selected in vitro 15 years ago from a pool of random RNA sequences catalyses formation of a 3′,5′-phosphodiester linkage analogous to a single step of RNA polymerization. Recently, the three-dimensional structure of the ligase was solved in complex with U1A RNA-binding protein and independently in complex with an antibody fragment. The RNA adopts a tripod arrangement and appears to use a two-metal ion mechanism similar to protein polymerases. Here, we discuss structural implications for engineering a true polymerase ribozyme and describe the use of the antibody framework both as a portable chaperone for crystallization of other RNAs and as a platform for exploring steps in evolution from the RNA world to the RNA–protein world.

scholarly journals G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2416 ◽  
Author(s):  
Mubarak I. Umar ◽  
Danyang Ji ◽  
Chun-Yin Chan ◽  
Chun Kit Kwok
Keyword(s):  
Interaction Mechanism ◽  
Rna Aptamers ◽  
Rna Sequences ◽  
Turn On ◽  
Dna And Rna ◽  
Cellular Events ◽  
Potential Applications ◽  
Micro Organisms ◽  
Nucleic Acid Structures

Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences. G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms. The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy. In addition to biophysical and biochemical methods to interrogate G4 formation, G4 fluorescent turn-on ligands can be used to target and visualize G4 formation both in vitro and in cells. Here, we review several representative classes of G4 fluorescent turn-on ligands in terms of their interaction mechanism and application perspectives. Interestingly, G4 structures are commonly identified in DNA and RNA aptamers against targets that include proteins and small molecules, which can be utilized as G4 tools for diverse applications. We therefore also summarize the recent development of G4-containing aptamers and highlight their applications in biosensing, bioimaging, and therapy. Moreover, we discuss the current challenges and future perspectives of G4 fluorescent turn-on ligands and G4-containing aptamers.

scholarly journals Aligning biological sequences by exploiting residue conservation and coevolution

2020 ◽  
Author(s):  
Anna Paola Muntoni ◽  
Andrea Pagnani ◽  
Martin Weigt ◽  
Francesco Zamponi
Keyword(s):  
Protein Interactions ◽  
Message Passing ◽  
Statistical Physics ◽  
Three Dimensional ◽  
Simulated Data ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Biological Sequences ◽  
Rna Sequences ◽  
And Function

Aligning biological sequences belongs to the most important problems in computational sequence analysis; it allows for detecting evolutionary relationships between sequences and for predicting biomolecular structure and function. Typically this is addressed through profile models, which capture position-specificities like conservation in sequences, but assume an independent evolution of different positions. RNA sequences are an exception where the coevolution of paired bases in the secondary structure is taken into account. Over the last years, it has been well established that coevolution is essential also in proteins for maintaining three-dimensional structure and function; modeling approaches based on inverse statistical physics can catch the coevolution signal and are now widely used in predicting protein structure, protein-protein interactions, and mutational landscapes. Here, we present DCAlign, an efficient approach based on an approximate message-passing strategy, which is able to overcome the limitations of profile models, to include general second-order interactions among positions and to be therefore universally applicable to protein- and RNA-sequence alignment. The potential of our algorithm is carefully explored using well-controlled simulated data, as well as real protein and RNA sequences.

scholarly journals The Role of RNA and DNA Aptamers in Glioblastoma Diagnosis and Therapy: A Systematic Review of the Literature

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2173 ◽  
Author(s):  
Silvia Nuzzo ◽  
Valentina Brancato ◽  
Alessandra Affinito ◽  
Marco Salvatore ◽  
Carlo Cavaliere ◽  
...  
Keyword(s):  
Systematic Review ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Primary Brain Tumor ◽  
Rna Aptamers ◽  
Diagnosis And Treatment ◽  
Dna And Rna ◽  
Therapeutic Tools ◽  
Oligonucleotide Library

Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional structures of single-stranded nucleic acids (RNA or DNA), identified by an in vitro process, named systematic evolution of ligands by exponential enrichment (SELEX), starting from a partially random oligonucleotide library. They bind to a molecular target with high affinity and specificity and can be easily modified to optimize binding affinity and selectivity. Thanks to their properties (low immunogenicity and toxicity, long stability, and low production variability), a large number of aptamers have been selected against GBM biomarkers and provide specific imaging agents and therapeutics to improve the diagnosis and treatment of GBM. However, the use of aptamers in GBM diagnosis and treatment still represents an underdeveloped topic, mainly due to limited literature in the research world. On these bases, we performed a systematic review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for GBM diagnosis and treatment. Thirty-eight studies from 2000 were included and investigated. Seventeen involved the use of aptamers for GBM diagnosis and 21 for GBM therapy. Our findings showed that a number of DNA and RNA aptamers are promising diagnostic and therapeutic tools for GBM management.

scholarly journals Evaluating DCA-based method performances for RNA contact prediction by a well-curated dataset

2019 ◽  
Author(s):  
F. Pucci ◽  
M. Zerihun ◽  
E. Peter ◽  
A. Schug
Keyword(s):  
Rna Structure ◽  
Structure Prediction ◽  
Sequence Data ◽  
Three Dimensional ◽  
Spatial Proximity ◽  
Dimensional Structure ◽  
Rna Sequences ◽  
Contact Prediction ◽  
Rna Molecules ◽  
Quality Of Structure

AbstractRNA molecules play many pivotal roles in the cellular functioning that are still not fully understood. Any detailed understanding of RNA function requires knowledge of its three-dimensional structure, yet experimental RNA structure resolution remains demanding. Recent advances in sequencing provide unprecedented amounts of sequence data that can be statistically analysed by methods such as Direct Coupling Analysis (DCA) to determine spatial proximity or contacts of specific nucleic acid pairs, which improve the quality of structure prediction. To quantify this structure prediction improvement, we here present a well curated dataset of about seventy RNA structures with high resolution and compare different nucleotide-nucleotide contact prediction methods available in the literature. We observe only minor difference between the performances of the different methods. Moreover, we discuss how these predictions are robust for different contact definitions and how strongly depend on procedures used to curate and align the families of homologous RNA sequences.

scholarly journals The Annotation of RNA Motifs

2002 ◽  
Vol 3 (6) ◽  
pp. 518-524 ◽  
Author(s):  
Neocles B. Leontis ◽  
Eric Westhof
Keyword(s):  
Protein Interactions ◽  
Rna Structure ◽  
Three Dimensional ◽  
Global Structure ◽  
Hierarchical Organization ◽  
Dimensional Structure ◽  
Base Pairs ◽  
Rna Motifs ◽  
Rna Sequences ◽  
Ordered Array

The recent deluge of new RNA structures, including complete atomic-resolution views of both subunits of the ribosome, has on the one hand literally overwhelmed our individual abilities to comprehend the diversity of RNA structure, and on the other hand presented us with new opportunities for comprehensive use of RNA sequences for comparative genetic, evolutionary and phylogenetic studies. Two concepts are key to understanding RNA structure: hierarchical organization of global structure and isostericity of local interactions. Global structure changes extremely slowly, as it relies on conserved long-range tertiary interactions. Tertiary RNA–RNA and quaternary RNA–protein interactions are mediated by RNA motifs, defined as recurrent and ordered arrays of non-Watson–Crick base-pairs. A single RNA motif comprises a family of sequences, all of which can fold into the same three-dimensional structure and can mediate the same interaction(s). The chemistry and geometry of base pairing constrain the evolution of motifs in such a way that random mutations that occur within motifs are accepted or rejected insofar as they can mediate a similar ordered array of interactions. The steps involved in the analysis and annotation of RNA motifs in 3D structures are: (a) decomposition of each motif into non-Watson–Crick base-pairs; (b) geometric classification of each basepair; (c) identification of isosteric substitutions for each basepair by comparison to isostericity matrices; (d) alignment of homologous sequences using the isostericity matrices to identify corresponding positions in the crystal structure; (e) acceptance or rejection of the null hypothesis that the motif is conserved.

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