A Single-Stranded DNA-Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks.
Adv Sci (Weinh)
; 7(22): 2001970, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-33240760
ABSTRACT
A versatile and Lipinski-compliant DNA-encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB-DEL library, constructed in single-stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single-stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self-assembled selectable chemical structures, leading to the identification of affinity-matured compounds.
DNAencoded chemical libraries (DEL); FANCD2associated nuclease 1 (FAN1); Human alphaaminoadipic semialdehyde synthase (AASS); affinity maturation; cyclicAMP response element binding protein (CREBBP); drug discovery; encoded selfassembling chemical libraries (ESAC); phosphatidylinositol 3kinase (PI3K)
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article