Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Bioconjug Chem ; 32(8): 1576-1580, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34346691

RESUMO

An efficient visible-light-induced alkylation of DNA-tagged quinoxaline-2-ones was described. The methodology demonstrated moderate-to-excellent conversions under mild conditions. The reaction was found to be tolerant with both N-protected α-amino acids and aliphatic carboxylic acids and could be applied to the synthesis of focused DNA-encoded quinoxalin-2-one libraries.


Assuntos
Ácidos Carboxílicos/química , DNA/química , Quinoxalinas/química , Alquilação/efeitos da radiação , Luz
2.
Bioconjug Chem ; 32(4): 685-689, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33720689

RESUMO

Thioethers have been widely found in biologically active compounds, including pharmaceuticals. In this report, a highly efficient approach to on-DNA construction of thioethers via Cu-promoted Ullmann cross-coupling between DNA-conjugated aryl iodides and thiols is developed. This methodology was demonstrated with medium to high yields, without obvious DNA damage. This reported reaction has strong potential for application in DNA-encoded chemical library synthesis.


Assuntos
DNA/química , Iodetos/química , Compostos de Sulfidrila/química
3.
RSC Med Chem ; 13(11): 1341-1349, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36426238

RESUMO

We describe a novel approach for screening fragments against a protein that combines the sensitivity of DNA-encoded library technology with the ability of fragments to explore what will bind. Each of the members of the library consists of a fragment which is linked to a photoactivatable diazirine moiety. Split and pool synthesis combines each fragment with a set of linkers with the version of the library reported here containing some 70k different compounds, each with an individual DNA code. Incubation of the library with a protein sample is followed by photoactivation, washing and subsequent PCR and sequencing which allows the individual fragment hits to be identified. We illustrate how the approach allows successful hit fragment identification using only microgram quantities of material for two targets. PAK4 is a kinase for which conventional fragment screening has generated many advance leads. The as yet undrugged target, 2-epimerase, presents a more challenging active site for identification of hit compounds. In both cases, PAC-FragmentDEL identified fragments validated as hits by ligand-observed NMR measurements and crystal structure determination of off-DNA sample binding to the proteins.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA