scholarly journals Molecular Modeling Applied to Nucleic Acid-Based Molecule Development

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 83 ◽  
Author(s):  
Arne Krüger ◽  
Flávia Zimbres ◽  
Thales Kronenberger ◽  
Carsten Wrenger
Keyword(s):  
Molecular Modeling ◽  
Nucleic Acid ◽  
Small Molecules ◽  
Structure Prediction ◽  
Rna Sequences ◽  
The Past ◽  
Enrichment Technique ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Early Drug

Molecular modeling by means of docking and molecular dynamics (MD) has become an integral part of early drug discovery projects, enabling the screening and enrichment of large libraries of small molecules. In the past decades, special emphasis was drawn to nucleic acid (NA)-based molecules in the fields of therapy, diagnosis, and drug delivery. Research has increased dramatically with the advent of the SELEX (systematic evolution of ligands by exponential enrichment) technique, which results in single-stranded DNA or RNA sequences that bind with high affinity and specificity to their targets. Herein, we discuss the role and contribution of docking and MD to the development and optimization of new nucleic acid-based molecules. This review focuses on the different approaches currently available for molecular modeling applied to NA interaction with proteins. We discuss topics ranging from structure prediction to docking and MD, highlighting their main advantages and limitations and the influence of flexibility on their calculations.

scholarly journals G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3781 ◽  
Author(s):  
Carolina Roxo ◽  
Weronika Kotkowiak ◽  
Anna Pasternak
Keyword(s):  
Nucleic Acid ◽  
Production Costs ◽  
Biological Processes ◽  
Disease Treatment ◽  
Diagnostic Potential ◽  
G Quadruplex ◽  
Fast Development ◽  
Systematic Evolution ◽  
Nucleic Acid Structures ◽  
Exponential Enrichment

G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.

scholarly journals Implementation of High-Throughput Sequencing (HTS) in Aptamer Selection Technology

2020 ◽  
Vol 21 (22) ◽  
pp. 8774
Author(s):  
Natalia Komarova ◽  
Daria Barkova ◽  
Alexander Kuznetsov
Keyword(s):  
Nucleic Acid ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Combinatorial Libraries ◽  
Structure And Function ◽  
Huge Number ◽  
Systematic Evolution ◽  
And Function ◽  
Exponential Enrichment

Aptamers are nucleic acid ligands that bind specifically to a target of interest. Aptamers have gained in popularity due to their high potential for different applications in analysis, diagnostics, and therapeutics. The procedure called systematic evolution of ligands by exponential enrichment (SELEX) is used for aptamer isolation from large nucleic acid combinatorial libraries. The huge number of unique sequences implemented in the in vitro evolution in the SELEX process imposes the necessity of performing extensive sequencing of the selected nucleic acid pools. High-throughput sequencing (HTS) meets this demand of SELEX. Analysis of the data obtained from sequencing of the libraries produced during and after aptamer isolation provides an informative basis for precise aptamer identification and for examining the structure and function of nucleic acid ligands. This review discusses the technical aspects and the potential of the integration of HTS with SELEX.

Aptamer Oligonucleotides as Potential Therapeutics in Hematologic Diseases

2019 ◽  
Vol 19 (10) ◽  
pp. 788-795
Author(s):  
Weibin Li ◽  
Meng Zhao ◽  
Huihui Yan ◽  
Kaiyu Wang ◽  
XIaopeng lan
Keyword(s):  
Clinical Trials ◽  
In Vitro Selection ◽  
Cell Disease ◽  
Anemia Of Chronic Disease ◽  
The Past ◽  
Systematic Evolution ◽  
Anemia Of Chronic Inflammation ◽  
Exponential Enrichment ◽  
Potential Therapeutics

: Aptamers are single-stranded DNA or RNA oligonucleotides generated by a novel in vitro selection technique termed Systematic evolution of ligands by exponential enrichment (SELEX). During the past two decades, various aptamer drugs have been developed and many of them have entered into clinical trials. : In the present review, we focus on aptamers as potential therapeutics for hematological diseases, including anemia of chronic inflammation (ACI) and anemia of chronic disease (ACD), hemophilia, thrombotic thrombocytopenic purpura (TTP) or VWD type-2B, and sickle cell disease (SCD), in particular, those that have entered into clinical trials

Modified Nucleic Acid for Systematic Evolution of RNA Ligands by Exponential Enrichment

1998 ◽  
Vol 13 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Yoshihiro Ito ◽  
Naozumi Teramoto ◽  
Naoki Kawazoe ◽  
Kojiro Inada ◽  
Yukio Imanishi
Keyword(s):  
Nucleic Acid ◽  
Systematic Evolution ◽  
Rna Ligands ◽  
Exponential Enrichment

scholarly journals Inside the Black Box: What Makes SELEX Better?

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3598 ◽  
Author(s):  
Natalia Komarova ◽  
Alexander Kuznetsov
Keyword(s):  
Nucleic Acid ◽  
Selection Process ◽  
Combinatorial Libraries ◽  
Black Box ◽  
Aptamer Selection ◽  
Selection Protocol ◽  
Systematic Evolution ◽  
Exponential Enrichment

Aptamers are small oligonucleotides that are capable of binding specifically to a target, with impressive potential for analysis, diagnostics, and therapeutics applications. Aptamers are isolated from large nucleic acid combinatorial libraries using an iterative selection process called SELEX (Systematic Evolution of Ligands by EXponential enrichment). Since being implemented 30 years ago, the SELEX protocol has undergone many modifications and improvements, but it remains a laborious, time-consuming, and costly method, and the results are not always successful. Each step in the aptamer selection protocol can influence its results. This review discusses key technical points of the SELEX procedure and their influence on the outcome of aptamer selection.

scholarly journals Identification of a response element in a herpesvirus saimiri mRNA recognized by the ORF57 protein

2009 ◽  
Vol 90 (3) ◽  
pp. 596-601 ◽  
Author(s):  
Kevin J. Colgan ◽  
James R. Boyne ◽  
Adrian Whitehouse
Keyword(s):  
Nuclear Export ◽  
Viral Rna ◽  
Herpesvirus Saimiri ◽  
Rna Sequences ◽  
Viral Mrnas ◽  
Response Element ◽  
Systematic Evolution ◽  
Exponential Enrichment

The herpesvirus saimiri (HVS) ORF57 protein binds viral RNA, enabling the efficient nuclear export of intronless viral mRNAs. However, it is not known how ORF57 recognizes these viral mRNAs. In this study, a systematic evolution of ligands by exponential enrichment (SELEX) approach was used to select RNA sequences that are preferentially bound by the ORF57 protein. Results identified a recurring motif, GAAGRG, within the majority of selected RNAs, which is also present in many late HVS mRNAs. RNA immunopreciptations demonstrated that disruption of this motif within a viral intronless RNA ablates ORF57 binding. These data suggest that the GAAGRG motif may be required within a HVS intronless mRNA for recognition by the ORF57 protein.

scholarly journals Preparation and Characterization of Aptamers Against O,p’-DDT

2020 ◽  
Vol 21 (6) ◽  
pp. 2211
Author(s):  
Wei Zhang ◽  
Danyang Li ◽  
Jianguang Zhang ◽  
Lingli Jiang ◽  
Zhaofa Li ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Small Molecules ◽  
Tap Water ◽  
Endocrine Disrupting Chemicals ◽  
Specific Probe ◽  
Endocrine Disrupting ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Dissociation Constant Kd

The compound 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p’-DDT) has been identified as one of the endocrine-disrupting chemicals causing adverse effects on wildlife and even humans through bioaccumulation. Its detection has become increasingly important. We have obtained candidate aptamers binding to o,p’-DDT by a systematic evolution of ligands by exponential enrichment (SELEX) protocol. Five out of seventeen candidate sequences were selected for preliminary characterization by SYBR Green I assay. One sequence with highest fluorescence response with o,p’-DDT, designated DDT_13, was chosen for further characterization. Its dissociation constant (Kd) was determined to be 412.3 ± 124.6 nM. DDT_13 exhibited low cross-binding activities on other tested small molecules. The good bioactivities of DDT_13 were demonstrated for the analysis of spiked lake water and tap water samples. This study provides a novel o,p’-DDT-specific probe for its future applications.

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