PEARL-seq: A Photoaffinity Platform for the Analysis of Small Molecule-RNA Interactions

被引：30

作者：

Mukherjee, Herschel ^{[1
]}

Blain, J. Craig ^{[1
]}

Vandivier, Lee E. ^{[1
]}

Chin, Donovan N. ^{[1
]}

Friedman, Jessica E. ^{[1
]}

Liu, Fei ^{[1
]}

Maillet, Ashley ^{[1
]}

Fang, Chao ^{[1
]}

Kaplan, Jenifer B. ^{[1
]}

Li, Jinxing ^{[2
]}

Chenoweth, David M. ^{[2
]}

Christensen, Allan Beck ^{[3
]}

Petersen, Lars Kolster ^{[3
]}

Hansen, Nils Jakob Vest ^{[3
]}

Barrera, Luis ^{[1
]}

Kubica, Neil ^{[1
]}

Kumaravel, Gnanasambandam ^{[1
]}

Petter, Jennifer C. ^{[1
]}

机构：

[1] Arrakis Therapeut, Waltham, MA 02451 USA

[2] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

[3] Vipergen, Copenhagen, Denmark

来源：

ACS CHEMICAL BIOLOGY | 2020年 / 15卷 / 09期

关键词：

SEQUENCE-BASED DESIGN; INDUCED FIT; TAR RNA; NMR; BINDING;

D O I：

10.1021/acschembio.0c00357

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small moleculeRNA interactions. Here, we present our efforts to develop such a platform using photoaffinity labeling. This technique, termed Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq), enables the rapid identification of small molecule binding locations within their RNA targets and can provide information on ligand selectivity across multiple different RNAs. These data, when supplemented with small molecule SAR data and RNA probing data enable the construction of a computational model of the RNA-ligand structure, thereby enabling the rational design of novel RNA-targeted ligands.

引用

页码：2374 / 2381

页数：8

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