X-aptamers: a bead-based selection method for random incorporation of druglike moieties onto next-generation aptamers for enhanced binding.
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.
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.
Weiguo
W
He
Miguel-Angel
MA
Elizondo-Riojas
Xin
X
Li
Ganesh Lakshmana Rao
GL
Lokesh
Anoma
A
Somasunderam
Varatharasa
V
Thiviyanathan
David E
DE
Volk
Ross H
RH
Durland
Johnnie
J
Englehardt
Claudio N
CN
Cavasotto
David G
DG
Gorenstein
D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D018960:Hyaluronan Receptors / Q000737:chemistry; D008024:Ligands; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011485:Protein Binding; D052156:SELEX Aptamer Technique / Q000379:methods*
D052157:Aptamers, Nucleotide; D018960:Hyaluronan Receptors; D008024:Ligands; C556788:N-acetyl-2,3-dehydro-2-deoxyneuraminic acid; D019158:N-Acetylneuraminic Acid