A Massively Parallel Selection of Small Molecule-RNA Motif Binding Partners Informs Design of an Antiviral from Sequence

被引：40

作者：

Childs-Disney, Jessica L. ^{[1
]}

Tuan Tran ^{[1
]}

Vummidi, Balayeshwanth R. ^{[1
]}

Velagapudi, Sai Pradeep ^{[1
]}

Haniff, Hafeez S. ^{[1
]}

Matsumoto, Yasumasa ^{[1
,4
]}

Crynen, Gogce ^{[2
]}

Southern, Mark R. ^{[2
]}

Biswas, Avik ^{[3
]}

Wang, Zi-Fu ^{[1
]}

Tellinghuisen, Timothy L. ^{[3
,5
]}

Disney, Matthew D. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA

[2] Scripps Res Inst, Informat Core, Jupiter, FL 33458 USA

[3] Scripps Res Inst, Dept Immunol & Infect Dis, Jupiter, FL 33458 USA

[4] Mitsubishi Tanabe Pharma Corp, Chuo Ku, 3-2-10 Dosho Machi, Osaka 5418505, Japan

[5] Roche Pharmaceut Res & Early Dev pRED, Dept Virol, Basel, Switzerland

来源：

CHEM | 2018年 / 4卷 / 10期

关键词：

WEST-NILE-VIRUS; 3 UNTRANSLATED REGION; DRUG DISCOVERY; INTERNAL LOOPS; SECONDARY STRUCTURE; DYSTROPHY TYPE-1; REPLICATION; IDENTIFY; GENOME; NUCLEOTIDES;

D O I：

10.1016/j.chempr.2018.08.003

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Many RNAs cause disease; however, RNA is rarely exploited as a small-molecule drug target. Our programmatic focus is to define privileged RNA motif small-molecule interactions to enable the rational design of compounds that modulate RNA biology starting from only sequence. We completed a massive, library-versus-library screen that probed over 50 million binding events between RNA motifs and small molecules. The resulting data provide a rich encyclopedia of small-molecule RNA recognition patterns, defining chemotypes and RNA motifs that confer selective, avid binding. The resulting interaction maps were mined against the entire viral genome of hepatitis C virus (HCV). A small molecule was identified that avidly bound RNA motifs present in the HCV 3' UTR and inhibited viral replication while having no effect on host cells. Collectively, this study represents the first whole-genome pattern recognition between small molecules and RNA folds.

引用

页码：2384 / 2404

页数：21

共 2 条

[1] Recognition of small molecule-RNA binding sites using RNA sequence and structure
Su, Hong
Peng, Zhenling
Yang, Jianyi
BIOINFORMATICS, 2021, 37 (01) : 36 - 42
[2] ISOLATION AND CHARACTERIZATION OF ESCHERICHIA-COLI MUTANTS AFFECTED IN AEROBIC RESPIRATION - THE CLONING AND NUCLEOTIDE-SEQUENCE OF UBIG IDENTIFICATION OF AN S-ADENOSYLMETHIONINE-BINDING MOTIF IN PROTEIN, RNA, AND SMALL-MOLECULE METHYLTRANSFERASES
WU, GH
WILLIAMS, HD
ZAMANIAN, M
GIBSON, F
POOLE, RK
JOURNAL OF GENERAL MICROBIOLOGY, 1992, 138 : 2101 - 2112

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