Hadi AlShamaileh, Rakesh N Veedu

Aptamers are single-stranded oligonucleotides (RNA or DNA) that can bind to their targets with high affinities and specificities because of their ability to adopt three-dimensional shapes in solution. Traditionally, aptamers are developed by SELEX (Systematic Evolution of Ligands by Exponential enrichment), a reiterative process involving selection by target molecule incubation with an oligonucleotide library and enrichment of the selected oligonucleotides by amplification. One drawback of current aptamer selection approach is the lack of diversity in the nucleic acid library with only four nucleobases compositions. Herein, we highlight a recent work that could successfully expanded the functional diversity of the starting oligonucleotide library by the introduction of pyrimidine nucleotides containing protein-like modifications at C5-position. The obtained results reinforce that enhancing the diversity of the starting library is indeed serve ways to evolve successful aptamers.