Challenges and Opportunities for Small Molecule Aptamer Development

Aptamers are single-stranded oligonucleotides that bind to targets with high affinity and selectivity. Their use as molecular recognition elements has emerged as a viable approach for biosensing, diagnostics, and therapeutics. Despite this potential, relatively few aptamers exist that bind to small molecules. Small molecules are important targets for investigation due to their diverse biological functions as well as their clinical and commercial uses. Novel, effective molecular recognition probes for these compounds are therefore of great interest. This paper will highlight the technical challenges of aptamer development for small molecule targets, as well as the opportunities that exist for their application in biosensing and chemical biology.

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Aptasensors for Small Molecule Detection

Zeitschrift für Naturforschung B ◽

10.5560/znb.2012-0147 ◽

2012 ◽

Vol 67 (10) ◽

pp. 976-986 ◽

Cited By ~ 22

Author(s):

Johanna-Gabriela Walter ◽

Alexandra Heilkenbrinker ◽

Jonas Austerjost ◽

Suna Timur ◽

Frank Stahl ◽

...

Keyword(s):

Molecular Recognition ◽

Small Molecules ◽

Small Molecule ◽

Conformational Changes ◽

Design Strategies ◽

Intelligent Sensors ◽

Biological Recognition ◽

Recognition Elements ◽

Small Molecule Detection

Aptamers are single-stranded oligonucleotides composed of RNA or DNA that are able to bind their corresponding targets via molecular recognition. Thus, aptamers can be thought of as nucleic acidbased alternatives to antibodies and have attracted attention as receptors in biosensors. Aptamers seem to be ideal biological recognition elements, since they enable the design of intelligent sensors based on their specific properties. Especially the fact that most aptamers undergo conformational changes during the binding of the target and their oligonucleotide nature can be used to rationally design novel sensing strategies. This review focuses on aptasensors for the detection of small molecules. In the first part, aptamers, their generation and their properties are briefly described. In the second part, different design strategies for aptasensors are reviewed, and examples for the detection of small molecules are given.

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RE-SELEX: Restriction Enzyme-Based Evolution of Structure-Switching Aptamer Biosensors

Chemical Science ◽

10.1039/d1sc02715h ◽

2021 ◽

Author(s):

Aimee Alice Sanford ◽

Alexandra E Rangel ◽

Trevor A Feagin ◽

Robert G Lowery ◽

Hector S Argueta-Gonzalez ◽

...

Keyword(s):

Small Molecule ◽

Restriction Enzyme ◽

High Affinity ◽

Recognition Elements ◽

Evolution Of Structure ◽

Structure Switching

Aptamers are widely employed as recognition elements in small molecule biosensors due to their ability to recognize small molecule targets with high affinity and selectivity. Structure-switching aptamers are particularly promising...

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In depth analysis of kinase cross screening data to identify chemical starting points for inhibition of the nek family of kinases

10.1101/137968 ◽

2017 ◽

Author(s):

Carrow I. Wells ◽

Nirav R. Kapadia ◽

Rafael M. Couñago ◽

David H. Drewry

Keyword(s):

Drug Discovery ◽

Small Molecules ◽

Small Molecule ◽

Kinase Inhibitors ◽

Biological Functions ◽

Chemical Probes ◽

High Quality ◽

Depth Analysis ◽

Number Of Citations ◽

Shed Light

AbstractPotent, selective, and cell active small molecule kinase inhibitors are useful tools to help unravel the complexities of kinase signaling. As the biological functions of individual kinases become better understood, they can become targets of drug discovery efforts. The small molecules used to shed light on function can also then serve as chemical starting points in these drug discovery efforts. The Nek family of kinases has received very little attention, as judged by number of citations in PubMed, yet they appear to play many key roles and have been implicated in disease. Here we present our work to identify high quality chemical starting points that have emerged due to the increased incidence of broad kinome screening. We anticipate that this analysis will allow the community to progress towards the generation of chemical probes and eventually drugs that target members of the Nek family.

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Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications

BioMed Research International ◽

10.1155/2015/419318 ◽

2015 ◽

Vol 2015 ◽

pp. 1-31 ◽

Cited By ~ 36

Author(s):

Ka Lok Hong ◽

Letha J. Sooter

Keyword(s):

Nucleic Acid ◽

Molecular Recognition ◽

Nucleic Acids ◽

Antibody Fragments ◽

Small Peptides ◽

Basic Principles ◽

Single Stranded Dna ◽

High Affinity ◽

Ssdna Aptamer ◽

Recognition Elements

Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed.

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Optimized methods for IL-17A refolding and anti-IL17A Fab production for co-crystallization with small molecules

BioTechniques ◽

10.2144/btn-2019-0170 ◽

2020 ◽

Vol 69 (1) ◽

pp. 70-76

Author(s):

Xiaoyun Meng ◽

Lanjun Zhang ◽

Hong Wei ◽

Furong Li ◽

Lihua Hu ◽

...

Keyword(s):

Drug Discovery ◽

Small Molecules ◽

Small Molecule ◽

Yield Enhancement ◽

High Affinity ◽

Interleukin 17A ◽

Affinity Peptide ◽

First Time ◽

Essential Prerequisite

Refolding of human interleukin 17A (IL-17A) has been reported; however, the key refolding protocol was not robust enough to deliver consistent results and to be easily scaled up for crystallization. Here we report an optimized refolding method for IL-17A. Although co-crystal structures of IL-17A with ligands have been obtained with a high-affinity peptide and an anti-IL-17A Fab as stabilizers, neither the production yield nor the characterization of the IL-17A/Fab complex was reported. To facilitate co-crystallization of IL-17A with small-molecule compounds derived from our DNA encoded library, we also describe the method for yield enhancement of anti-IL-17A Fab production and characterize the IL-17A/Fab complex for the first time, providing an essential prerequisite for structure-based drug discovery targeting IL-17A.

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Current Status and Future Prospects for Aptamer-Based Mycotoxin Detection

Journal of AOAC International ◽

10.5740/jaoacint.16-0114 ◽

2016 ◽

Vol 99 (4) ◽

pp. 865-877 ◽

Cited By ~ 12

Author(s):

Annamaria Ruscito ◽

McKenzie Smith ◽

Daniel N Goudreau ◽

Maria C DeRosa

Keyword(s):

Molecular Recognition ◽

Review Article ◽

Current Status ◽

Future Prospects ◽

High Affinity ◽

The Past ◽

Recognition Elements ◽

Target Analyte

Abstract Aptamers are single-stranded oligonucleotides with the ability to bind tightly and selectively to a target analyte. High-affinity and specific aptamers for a variety of mycotoxins have been reported over the past decade. Increasingly, these molecular recognition elements are finding applications in biosensors and assays for the detection of mycotoxins in a variety of complex matrixes. This review article highlights the mycotoxin aptamers that are available for mycotoxin detection and the array of biosensing platforms into which they have been incorporated. Key advantages that aptamers have over analogous technology, and areas in which these advantages may be applied for the benefit of practical mycotoxin detection, are also discussed.

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DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules

Chemical Science ◽

10.1039/c4sc01654h ◽

2015 ◽

Vol 6 (1) ◽

pp. 739-744 ◽

Cited By ~ 53

Author(s):

J.-P. Daguer ◽

C. Zambaldo ◽

M. Ciobanu ◽

P. Morieux ◽

S. Barluenga ◽

...

Keyword(s):

Small Molecules ◽

Small Molecule ◽

Biologically Active ◽

High Affinity ◽

Affinity Ligand ◽

High Affinity Ligand

A focused library for Hsp70 was prepared from fragments identified from an array combinatorially pairing two libraries of small molecule fragments. Screening of the focus library yielded high affinity ligand to Hsp70.

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In VitroSelection of a Single-Stranded DNA Molecular Recognition Element Specific for Bromacil

Journal of Nucleic Acids ◽

10.1155/2014/102968 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Ryan M. Williams ◽

Amanda R. Kulick ◽

Srilakshmi Yedlapalli ◽

Louisa Battistella ◽

Cyrus J. Hajiran ◽

...

Keyword(s):

Molecular Recognition ◽

Selection Method ◽

Detection Methods ◽

Sensing Element ◽

Single Stranded Dna ◽

Recognition Element ◽

High Affinity ◽

Recognition Elements ◽

Molecular Recognition Element

Bromacil is a widely used herbicide that is known to contaminate environmental systems. Due to the hazards it presents and inefficient detection methods, it is necessary to create a rapid and efficient sensing device. Towards this end, we have utilized a stringentin vitroselection method to identify single-stranded DNA molecular recognition elements (MRE) specific for bromacil. We have identified one MRE with high affinity (Kd=9.6 nM) and specificity for bromacil compared to negative targets of selection and other pesticides. The selected ssDNA MRE will be useful as the sensing element in a field-deployable bromacil detection device.

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