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

详细信息    查看全文

• 作者：Yizhou Li ; Elena Gabriele ; Florent Samain ; Nicholas Favalli ; Filippo Sladojevich ; Jörg Scheuermann ; Dario Neri
• 刊名：ACS Combinatorial Science
• 出版年：2016
• 出版时间：August 8, 2016
• 年：2016
• 卷：18
• 期：8
• 页码：438-443
• 全文大小：352K
• 年卷期：0
• ISSN：2156-8944

文摘

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