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    Nmr spectroscopy for probing the structural determinants of aptamer optimization and riboswitch engineering
    (Bentham Science Publishers, 2020) Bora B.; Uğurlu Ö.; Man E.; Gültan M.; Özyurt C.; Evran S.
    Nucleic acid aptamers are single-stranded DNA or RNA molecules that can fold into unique conformations and specifically recognize various targets, such as small molecules, proteins, cells, and tissues. Aptamers are selected in vitro through an iterative process called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). As aptamers possess several advantages over antibodies, several diagnostic and therapeutic applications have emerged in recent years. Aptamers also attract interest as they form the receptor domain of RNA-based riboswitches that function as natural modulators of gene expression. Aptamer domain of riboswitch can sense the metabolite and this binding event is transduced into a conformational change, thereby transcriptional or translational control is achieved. Riboswitch engineering has gained importance due to the potential use of artificial riboswitches in biosensors and next- generation therapeutics. Therefore, understanding the structural basis of ligand binding and conformational change is critical for the success of optimization or re-engineering of aptamers. Since crystallization of aptamer-small molecule target complexes is particularly difficult, NMR provides an indispensable tool for structural analysis. In this chapter, we first give a brief information about aptamers and riboswitches. Then, we review the NMR structures of aptamers and riboswitches reported to date. We highlight the importance of NMR for identification of ligand binding mechanism, post-SELEX optimization of aptamers, as well as for the design of artificial riboswitches. In this context, we also give some examples of aptamer studies involving a combination of NMR and other techniques. © 2020 Bentham Science Publishers.
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    Nucleic Acid and Peptide Aptamers as Potential Antiviral Drugs
    (Bentham Science Publishers, 2021) Evran S.; Uğurlu Ö.; Man E.; Gültan M.; Özyurt C.
    Aptamers with target-specific binding properties have emerged as an alternative to antibodies. Nucleic acid aptamers are short single-stranded oligonucleotides that can fold into unique three-dimensional structures. Nucleic acid aptamers are selected from random libraries in vitro by using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology. Likewise, peptide aptamers are short peptides that can be selected in vitro by using different strategies including phage display, ribosome display, or mRNA display. Aptamers are superior to antibodies with regard to ease of production, high stability, small size, and low cost. Therefore, aptamers find broad use in different biotechnological and therapeutic applications. Among them, aptamer use in virus detection and antiviral therapy is one of the attractive applications. The present Covid-19 pandemic and life-threatening viral infections reveal the need for rapid therapeutic solutions that can efficiently target viral mechanisms. In this respect, the chapter is mainly focused on aptamers with antiviral activity, as well as the use of aptamers in viral detection platforms. First, we summarize aptamer selection technologies that can be performed in vitro. Among them, we briefly explain ribosome display, mRNA display and SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technologies. Then, we review aptamers targeting viral proteins and viral invasion mechanisms. In addition, we give an overview of aptamers developed against viruses. We also discuss the major hurdles in aptamer use, as well as the strategies to improve the drug potential of aptamers. © 2021 Bentham Science Publishers.