title: Stability of Oligonucleotide-Small Molecule Conjugates to DNA-Deprotection Conditions.
abstract: Oligonucleotide conjugates of small molecules are widely used in chemical biology and have found increasing interest in the context of DNA-encoded chemical libraries for drug discovery. Attachment of molecules to DNA bound to the solid support is an attractive small-molecule conjugation method that permits the use of organic solvents, rigorous reaction conditions, and simple workup. However, the conjugated structures must be resistant to the harsh DNA deprotection/cleavage conditions and the stabilities of building blocks under various deprotection conditions are mostly unexplored. In the present study, we analyzed the stability of 131 structurally diverse fragments that contain amides and amide-like elements during DNA deprotection protocols. Structural features susceptible to decomposition in DNA deprotection conditions were identified and a protocol that enabled the synthesis of DNA conjugates with labile fragments on solid support was identified.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah , 30 S 2000 E, Salt Lake City, Utah 84112, United States.
authors.forename: Lik Hang
authors.initials: LH
authors.lastname: Yuen
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah , 30 S 2000 E, Salt Lake City, Utah 84112, United States.
authors.forename: Raphael M
authors.identifier: 0000-0001-6772-5119
authors.initials: RM
authors.lastname: Franzini
mesh_terms: D000577:Amides / Q000737:chemistry; D053837:DNA Cleavage; D055808:Drug Discovery; D004355:Drug Stability; D009841:Oligonucleotides / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D000577:Amides; D009841:Oligonucleotides; D054852:Small Molecule Libraries