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Methods for Improving Aptamer Binding Affinity

Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamer...

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Autores principales: Hasegawa, Hijiri, Savory, Nasa, Abe, Koichi, Ikebukuro, Kazunori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273865/
https://www.ncbi.nlm.nih.gov/pubmed/27043498
http://dx.doi.org/10.3390/molecules21040421
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author Hasegawa, Hijiri
Savory, Nasa
Abe, Koichi
Ikebukuro, Kazunori
author_facet Hasegawa, Hijiri
Savory, Nasa
Abe, Koichi
Ikebukuro, Kazunori
author_sort Hasegawa, Hijiri
collection PubMed
description Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of aptamers. In particular, sequence optimization using combined in silico sequence recombinations and in vitro functional evaluations is effective for the improvement of binding affinities, however, the binding affinities of aptamers are limited by the low hydrophobicity of nucleic acids. Accordingly, introduction of hydrophobic moieties into aptamers expands the diversity of interactions between aptamers and targets. Moreover, construction of multivalent aptamers by connecting aptamers that recognize distinct epitopes is an attractive approach to substantial increases in binding affinity. In addition, binding affinities can be tuned by optimizing the scaffolds of multivalent constructs. In this review, we summarize the various techniques for improving the binding affinities of aptamers.
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spelling pubmed-62738652018-12-28 Methods for Improving Aptamer Binding Affinity Hasegawa, Hijiri Savory, Nasa Abe, Koichi Ikebukuro, Kazunori Molecules Review Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of aptamers. In particular, sequence optimization using combined in silico sequence recombinations and in vitro functional evaluations is effective for the improvement of binding affinities, however, the binding affinities of aptamers are limited by the low hydrophobicity of nucleic acids. Accordingly, introduction of hydrophobic moieties into aptamers expands the diversity of interactions between aptamers and targets. Moreover, construction of multivalent aptamers by connecting aptamers that recognize distinct epitopes is an attractive approach to substantial increases in binding affinity. In addition, binding affinities can be tuned by optimizing the scaffolds of multivalent constructs. In this review, we summarize the various techniques for improving the binding affinities of aptamers. MDPI 2016-03-28 /pmc/articles/PMC6273865/ /pubmed/27043498 http://dx.doi.org/10.3390/molecules21040421 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hasegawa, Hijiri
Savory, Nasa
Abe, Koichi
Ikebukuro, Kazunori
Methods for Improving Aptamer Binding Affinity
title Methods for Improving Aptamer Binding Affinity
title_full Methods for Improving Aptamer Binding Affinity
title_fullStr Methods for Improving Aptamer Binding Affinity
title_full_unstemmed Methods for Improving Aptamer Binding Affinity
title_short Methods for Improving Aptamer Binding Affinity
title_sort methods for improving aptamer binding affinity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273865/
https://www.ncbi.nlm.nih.gov/pubmed/27043498
http://dx.doi.org/10.3390/molecules21040421
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