Comparative evaluation of DNA-encoded chemical selections performed using DNA in single-stranded or double-stranded format.
Biochem Biophys Res Commun
; 533(2): 223-229, 2020 12 03.
Article
em En
| MEDLINE
| ID: mdl-32386812
ABSTRACT
DNA-encoded chemical libraries (DEL) are increasingly being used for the discovery and optimization of small organic ligands to proteins of biological or pharmaceutical interest. The DNA fragments, that serve as amplifiable identification barcodes for individual compounds in the library, are typically used in double-stranded DNA format. To the best of our knowledge, a direct comparison of DEL selections featuring DNA in either single- or double-stranded DNA format has not yet been reported. In this article, we describe a comparative evaluation of selections with two DEL libraries (named GB-DEL and NF-DEL), based on different chemical designs and produced in both single- and double-stranded DNA format. The libraries were selected in identical conditions against multiple protein targets, revealing comparable and reproducible fingerprints for both types of DNA formats. Surprisingly, selections performed with single-stranded DNA barcodes exhibited improved enrichment factors compared to double-stranded DNA. Using high-affinity ligands to carbonic anhydrase IX as benchmarks for selection performance, we observed an improved selectivity for the NF-DEL library (on average 2-fold higher enrichment factors) in favor of single-stranded DNA. The enrichment factors were even higher for the GB-DEL selections (approximately 5-fold), compared to the same library in double-stranded DNA format. Collectively, these results indicate that DEL libraries can conveniently be synthesized and screened in both single- and double-stranded DNA format, but single-stranded DNA barcodes typically yield enhanced enrichment factors.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
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DNA de Cadeia Simples
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Bibliotecas de Moléculas Pequenas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article