X-Aptamers: A Bead-Based Selection Method for Random Incorporation of Druglike Moieties onto Next-Generation Aptamers for Enhanced Binding

HE, W.; ELIZONDO-ROJAS, M.A.; LI, X.; LOKESH, G.; SOMASUNDERAM, A.; THIVIYANATHAN, V.; VOLK, D.E.; DURLAND, R.H.; ENGLEHARDT, J.; CAVASOTTO, CLAUDIO NORBERTO; GORENSTEIN, DAVID G.

BIOCHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2012 vol. 51 p. 8321 - 8323

0006-2960

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.