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Challenges and Opportunities for Small Molecule Aptamer Development

DOI: 10.1155/2012/748913

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Abstract:

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. 1. Aptamers as Molecular Recognition Elements Historically, nucleic acids were associated with the storage and genetic coding of information and have long been thought to be less complex than proteins [1]. However, like proteins, nucleic acids are able to fold into intricate tertiary structures that have the potential to perform a variety of functions including gene-regulation, catalytic activity and ligand-binding [2]. Interest in these so-called “functional” nucleic acids was prompted by the ever-increasing number of discoveries of non-coding ribonucleic acids (RNAs) displaying catalytic or binding properties [2]. Two decades ago, several researchers revolutionized molecular recognition by developing synthetic RNA motifs that bound specifically to molecular targets [3–5]. These RNA structures, called aptamers, were selected using an in vitro selection procedure called systematic evolution of ligands by exponential enrichment (SELEX) [3]. Like antibodies, these synthetically derived molecular recognition probes were found to be selective and able to bind to their targets with high affinity. Currently, there is a growing need for rapid, robust, and inexpensive methods for sensing and diagnostic purposes [6]. As molecular recognition is the cornerstone of sensing, there has been increased focus on the development of new molecular recognition probes for sensing applications [7]. While antibodies have long been considered to be the standard in molecular recognition and the use of antibodies as recognition probes predates the 1950s, the relatively new technology of aptamers offers several advantages [8]. Firstly, the in vitro aptamer selection process allows a greater control over aptamer binding conditions. Nonphysiological salt concentrations, temperatures and pH can be used in successful selections [9]. Due to the

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