Therapeutic Potential of Aptamer–Protein Interactions

Abstract

Aptamers are single-stranded oligonucleotides (RNA or DNA) with a typical length between 25 and 100 nucleotides which fold into three-dimensional structures capable of binding to target molecules. Specific aptamers can be isolated against a large variety of targets through efficient and relatively cheap methods, and they demonstrate target-binding affinities that sometimes surpass those of antibodies. Consequently, interest in aptamers has surged over the past three decades, and their application has shown promise in advancing knowledge in target analysis, designing therapeutic interventions, and bioengineering. With emphasis on their therapeutic applications, aptamers are emerging as a new innovative class of therapeutic agents with promising biochemical and biological properties. Aptamers have the potential of providing a feasible alternative to antibody-and small-molecule-based therapeutics given their binding specificity, stability, low toxicity, and apparent non-immunogenicity. This Review examines the general properties of aptamers and aptamer− protein interactions that help to understand their binding characteristics and make them important therapeutic candidates.

Dynamics of Protein–RNA Interfaces Using All-Atom Molecular Dynamics Simulations

“…In other words, the stability of the complex is due to different patterns of contacts without strongly affecting the protein conformation. While the RNA aptamer is not natural, it binds the NF-κB with high affinity and it has been suggested to be a promising therapeutics capable of inhibiting the NF-κB transcriptor factor. , Hence, the identification of alternative interface substates allows us to determine the different contacts in terms of base pairing and stacking, for example. These pieces of information are not accessible via X-ray crystallography, like the highly dynamics of the protein–RNA interface.…”

The dynamics of protein-RNA interfaces using all-atom molecular dynamics simulations

“…While the RNA aptamer is not natural, it binds the NF- κ B with high affinity and it has been suggested to be a promising therapeutics capable to inhibit the NF- κ B transcriptor factor. 100,101 Hence, the identification of alternative interface substates allows us to determine the different contacts in terms of base pairing and stacking for example. These pieces of information are not accessible via x-ray crystallography, like the highly dynamics of the protein-RNA interface.…”

Unique quinoline orientations shape the modified aptamer to sclerostin for enhanced binding affinity and bone anabolic potential

“…Aptamers are usually selected from pools of randomly synthesized oligodeoxynucleotides or oligonucleotides using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology. 1 In comparison with antibodies, aptamers are increasingly emerging as a powerful alternative due to their ease of synthesis, low immunogenicity, high stability, and broad range of target recognition. 2 Although researchers have developed thousands of aptamers against various targets in basic research, 3 only two aptamers (pegaptanib against vascular endothelial growth factor, 4 and izervay against C5) have been approved by the U.S. Food and Drug Administration.…”