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1.
Chem Commun (Camb) ; 56(24): 3563-3566, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32104845

RESUMO

An iridium catalyzed method for the synthesis of saturated aza-heterocycles from amines and diols is reported. A wide range of substituted heterocycles can be obtained using this approach including products bearing substituents at the C2, C3 and C4 positions. Employing water as the solvent, enantiopure diols could undergo annulation with minimal racemization, enabling the synthesis of valuable enantioenriched C3 and C4-substituted saturated aza-heterocycles.

2.
Angew Chem Int Ed Engl ; 58(50): 17930-17952, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-30633431

RESUMO

Epigenetics is currently the focus of intense research interest across a broad range of disciplines due to its importance in a multitude of biological processes and disease states. Epigenetic functions result partly from modification of the nucleobases in DNA and RNA, and/or post-translational modifications of histone proteins. These modifications are dynamic, with cellular machinery identified to modulate and interpret the marks. Our focus is on bromodomains, which bind to acetylated lysine residues. Progress in the study of bromodomains, and the development of bromodomain ligands, has been rapid. These advances have been underpinned by many disciplines, but chemistry and chemical biology have undoubtedly played a significant role. Herein, we review the key chemistry and chemical biology approaches that have furthered our study of bromodomains, enabled the development of bromodomain ligands, and played a critical role in the validation of bromodomains as therapeutic targets.


Assuntos
Epigenômica/métodos , Biologia Molecular/métodos , Domínios Proteicos/genética , Acetilação , Aminoácidos/química , Aminoácidos/metabolismo , Sistemas CRISPR-Cas , Epigênese Genética , Histonas/metabolismo , Ligantes , Lisina/metabolismo , Espectroscopia de Ressonância Magnética , Sondas Moleculares/química , Testes de Mutagenicidade
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