Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries

• DOI: 10.1021/acscombsci.6b00058
• Publication Date: 2016-06-17T20:18:36Z
• Authors: Yizhou Li; Elena Gabriele; Florent Samain; Nicholas Favalli; Filippo Sladojevich; Jörg Scheuermann; Dario Neri
• Keywords: Carbodiimide; Amide

DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins biological or pharmaceutical interest. In majority cases, synthetic procedures formation incorporate at least one step amide bond between amino-modified DNA and a carboxylic acid. We investigated reaction conditions established methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% 423/543 (78%) acids tested. These were efficient with variety primary secondary amines, well various types oligonucleotides. The conditions, also worked efficiently over broad range concentrations scales, should facilitate synthesis novel libraries.