“Cap-and-Catch” Purification for Enhancing
the Quality of Libraries of DNA Conjugates
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Abstract
The potential of DNA-encoded combinatorial
libraries (DECLs) as
tools for hit discovery crucially relies on the availability of methods
for their synthesis at acceptable purity and quality. Incomplete reactions
in the presence of DNA can noticeably affect the purity of DECLs and
methods to selectively remove unreacted oligonucleotide-based starting
products would likely enhance the quality of DECL screening results.
We describe an approach to selectively remove unreacted oligonucleotide
starting products from reaction mixtures and demonstrate its applicability
in the context of acylation of amino-modified DNA. Following an amide
bond forming reaction, we treat unreacted amino-modified DNAs with
biotinylating reagents and isolate the corresponding biotinylated
oligonucleotides from the reaction mixture by affinity capture on
streptavidin-coated sepharose. This approach, which yields the desired
DNA-conjugate at enhanced purity, can be applied both to reactions
performed in solution and to procedures in which DNA is immobilized
on an anion exchange solid support