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.
Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries / Y. Li, E. Gabriele, F. Samain, N. Favalli, F. Sladojevich, J. Scheuermann, D. Neri. - In: ACS COMBINATORIAL SCIENCE. - ISSN 2156-8952. - 18:8(2016 Aug), pp. 438-443.
|Titolo:||Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries|
GABRIELE, ELENA (Primo)
|Parole Chiave:||amide bond formation; bioconjugation; DNA-encoded chemical libraries; synthesis|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||ago-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acscombsci.6b00058|
|Appare nelle tipologie:||01 - Articolo su periodico|