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Biochemistry. 2012 Oct 23;51(42):8321-3. doi: 10.1021/bi300471d. Epub 2012 Oct 11.

X-aptamers: a bead-based selection method for random incorporation of druglike moieties onto next-generation aptamers for enhanced binding.

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Center for Proteomics and Systems Biology, The Brown Foundation Institute for Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center, 1825 Pressler Street, Houston, TX 77030, USA.

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  • Biochemistry. 2012 Nov 27;51(47):9592.


By combining pseudorandom bead-based aptamer libraries with conjugation chemistry, we have created next-generation aptamers, X-aptamers (XAs). Several X-ligands can be added in a directed or random fashion to the aptamers to further enhance their binding affinities for the target proteins. Here we describe the addition of a drug (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), demonstrated to bind to CD44-HABD, to a complete monothioate backbone-substituted aptamer to increase its binding affinity for the target protein by up to 23-fold, while increasing the drug's level of binding 1-million fold.

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