Chemical Knockdown of MicroRNA with Small-Molecule Chimeras

被引：2

作者：

Feng, Yi ^{[1
]}

Li, Jinbo ^{[1
]}

Zhang, Yan ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Analyt Chem Life Sci, Jiangsu Key Lab Adv Organ Mat, Sch Chem & Chem Engn,Chem & Biomed Innovat Ctr, Nanjing 210023, Peoples R China

来源：

CHEMBIOCHEM | 2020年 / 21卷 / 22期

基金：

中国国家自然科学基金;

关键词：

cancer therapy; microRNA; small-molecule binders; small-molecule chimeras; targeted degradation; SEQUENCE-BASED DESIGN; RNA; TARGET; RECOGNITION; CANCER; THERAPEUTICS; INHIBITION; CLEAVAGE;

D O I：

10.1002/cbic.202000287

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：

This concept article introduces the emerging area of small-molecule chimeras (SMCs) for knocking down microRNAs (miRNAs), which are endogenous gene silencers involved in diverse pathological processes. Compared with agents for genetic knockdown, small-molecules hold significant promise in this field due to their ideal pharmacokinetic and pharmacodynamic properties. The SMCs introduced here are hetero-bifunctional molecules comprising small-molecule binders (SMBs) of miRNAs and chemical functionalities that either directly cleave RNAs or recruit ribonucleases to destroy RNAs. Binding of SMBs to miRNAs brings SMCs' chemical functionalities close to the miRNA, eventually causing miRNA degradation. Compared with parent SMBs, SMCs exhibit remarkably enhanced potency and specificity in miRNA inhibition. The development and application of SMCs for miRNAs will be discussed.

引用

页码：3180 / 3185

页数：6

共 40 条

[21] Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells [J].

Guttilla, Irene K. ;

White, Bruce A. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (35) :23204-23216

[22] Regulation of microRNA biogenesis [J].

Ha, Minju ;

Kim, V. Narry .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (08) :509-524

[23] Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling [J].

Haga, Christopher L. ;

Velagapudi, Sai Pradeep ;

Strivelli, Jacqueline R. ;

Yang, Wang-Yong ;

Disney, Matthew D. ;

Phinney, Donald G. .

ACS CHEMICAL BIOLOGY, 2015, 10 (10) :2267-2276

[24] miR-21: a small multi-faceted RNA [J].

Krichevsky, Anna M. ;

Gabriely, Galina .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (01) :x-53

[25] MicroRNAs as novel biological targets for detection and regulation [J].

Li, Jinbo ;

Tan, Subee ;

Kooger, Romain ;

Zhang, Chenyu ;

Zhang, Yan .

CHEMICAL SOCIETY REVIEWS, 2014, 43 (02) :506-517

[26] Precise Small Molecule Degradation of a Noncoding RNA Identifies Cellular Binding Sites and Modulates an Oncogenic Phenotype [J].

Li, Yue ;

Disney, Matthew D. .

ACS CHEMICAL BIOLOGY, 2018, 13 (11) :3065-3071

[27] Therapeutic targeting of microRNAs: current status and future challenges [J].

Li, Zhonghan ;

Rana, Tariq M. .

NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (08) :622-638

[28] MicroRNA biogenesis pathways in cancer [J].

Lin, Shuibin ;

Gregory, Richard I. .

NATURE REVIEWS CANCER, 2015, 15 (06) :321-333

[29] Targeted Degradation of the Oncogenic MicroRNA 17-92 Cluster by Structure-Targeting Ligands [J].

Liu, Xiaohui ;

Haniff, Hafeez S. ;

Childs-Disney, Jessica L. ;

Shuster, Anton ;

Aikawa, Haruo ;

Adibekian, Alexander ;

Disney, Matthew D. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2020, 142 (15) :6970-6982

[30] Cleavage of RNA phosphodiester bonds by small molecular entities: a mechanistic insight [J].

Lonnberg, Harri .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2011, 9 (06) :1687-1703

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