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

ABSTRACT: 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.

SUBMITTER: He W

PROVIDER: S-EPMC3924539 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

He Weiguo W Elizondo-Riojas Miguel-Angel MA Li Xin X Lokesh Ganesh Lakshmana Rao GL Somasunderam Anoma A Thiviyanathan Varatharasa V Volk David E DE Durland Ross H RH Englehardt Johnnie J Cavasotto Claudio N CN Gorenstein David G DG

Biochemistry 20121011 42

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 ...[more]

PMID: 23057694

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