title: "Cap-and-Catch" Purification for Enhancing the Quality of Libraries of DNA Conjugates.
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.
authors.affiliation: †Institute of Pharmaceutical Sciences, ETH Zürich Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Raphael M
authors.initials: RM
authors.lastname: Franzini
authors.affiliation: †Institute of Pharmaceutical Sciences, ETH Zürich Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Biendl
authors.affiliation: ‡Philochem AG, Libernstrasse 3, 8112 Otelfingen, Switzerland.
authors.forename: Gediminas
authors.initials: G
authors.lastname: Mikutis
authors.affiliation: ‡Philochem AG, Libernstrasse 3, 8112 Otelfingen, Switzerland.
authors.forename: Florent
authors.initials: F
authors.lastname: Samain
authors.affiliation: †Institute of Pharmaceutical Sciences, ETH Zürich Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheuermann
authors.affiliation: †Institute of Pharmaceutical Sciences, ETH Zürich Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D000577:Amides / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification*; D015394:Molecular Structure
chemical_list: D000577:Amides; D004247:DNA
keywords: DNA-encoded chemical libraries; bioconjugation; biotin; purification