A Single-Stranded DNA-Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks

被引：40

作者：

Bassi, Gabriele ^{[1
]}

Favalli, Nicholas ^{[1
]}

Vuk, Miriam ^{[1
]}

Catalano, Marco ^{[1
]}

Martinelli, Adriano ^{[1
]}

Trenner, Anika ^{[2
]}

Porro, Antonio ^{[2
]}

Yang, Su ^{[3
]}

Tham, Chuin Lean ^{[4
]}

Moroglu, Mustafa ^{[5
]}

Yue, Wyatt W. ^{[4
]}

Conway, Stuart J. ^{[5
]}

Vogt, Peter K. ^{[3
]}

Sartori, Alessandro A. ^{[2
]}

Scheuermann, Joerg ^{[1
]}

Neri, Dario ^{[1
]}

机构：

[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8092 Zurich, Switzerland

[2] Univ Zurich, Inst Mol Canc Res, CH-8006 Zurich, Switzerland

[3] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA

[4] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium SGC, Oxford OX1 2JD, England

[5] Univ Oxford, Chem Res Lab, Dept Chem, Mansfield Rd, Oxford OX1 3TA, England

来源：

ADVANCED SCIENCE | 2020年 / 7卷 / 22期

基金：

瑞士国家科学基金会; 加拿大创新基金会; 英国工程与自然科学研究理事会; 巴西圣保罗研究基金会; 英国惠康基金; 欧洲研究理事会;

关键词：

Human alpha-aminoadipic semialdehyde synthase (AASS); affinity maturation; cyclic-AMP response element binding protein (CREBBP); DNA-encoded chemical libraries (DEL); drug discovery; encoded self-assembling chemical libraries (ESAC); FANCD2-associated nuclease 1 (FAN-1); phosphatidylinositol 3-kinase (PI3K); SMALL MOLECULES; BINDING-MOLECULES; TARGET PAIRS; IDENTIFICATION; INHIBITORS; AFFINITY; SELECTION; PI3K; ANTAGONISTS; NUCLEASE;

D O I：

10.1002/advs.202001970

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：10

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