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Abstract

The present invention relates to methods for producing encoded chemical entities. In particular, the oligonucleotides and methods can include encoded chemical entities having wild-type linkages formed through chemical ligation techniques. One strategy that can be utilized that simultaneously takes advantage of chemical ligation as a means to encode chemical history, while also retaining the ability of polymerases to directly recover tag sequence and association information, is to perform chemical ligation in a manner that generates wildtype phosphodiester linkages. Such methods generally utilize condensing agents such as cyanogen bromide or similar along with 5′-phosphate and 3′-hydroxyl oligonucleotides in a double-stranded or templated context. Similarly cyanogen bromide has also been shown to chemically ligate pairs of substrate oligonucleotides that are 5′-hydroxyl and 3′-phosphate. However, these methods suffer from poor efficiency making them ill-suited for use in an iterative process such as tagging DNA-en-coded libraries.

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First Claim