The Interactions of Small Molecules with DNA and RNA

Xie, Yun; Tam, Victor K.; Tor, Yitzhak

doi:10.1002/9780470664001.ch6

Cited by 17 publications

(8 citation statements)

References 128 publications

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“…This makes RNA less likely to bind proteins via hydrophobic interactions, compared to DNA. Small molecules usually bind to the deeper and narrower major groove of RNA which possesses a larger electrostatic potential [23].…”

Section: Interactionsmentioning

confidence: 99%

Challenges and current status of computational methods for docking small molecules to nucleic acids

Luo

Wei

Waldispühl

et al. 2019

European Journal of Medicinal Chemistry

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Since the development of the first docking program in 1982, their use in in silico screening for potentially bioactive molecule discovery has become a common strategy in academia and pharmaceutical industry. Up until recently, their use has largely focused on drugs binding to proteins. However, with the relatively recent discovery of promising drug targets in nucleic acids, including RNA riboswitches, DNA G-quadruplexes, and extended repeats in RNA, there has been a greater interest in developing drugs for nucleic acids. However, due to the major biochemical and physical differences in charges, binding pockets, and solvation, existing docking programs, developed for proteins, face difficulties when adopted directly for nucleic acids. In this review, we cover the current field of in silico docking to nucleic acids, available programs, as well as challenges faced in the field.

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Section: Interactionsmentioning

confidence: 99%

Challenges and current status of computational methods for docking small molecules to nucleic acids

Luo

Wei

Waldispühl

et al. 2019

European Journal of Medicinal Chemistry

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“…Small molecules interact with DNA through either intercalation or groove‐binding interactions, although it should be noted that some compounds can bind to DNA via a combination of both binding modes. Comprehensive reviews have been published on small molecule–DNA interactions …”

Section: Dna‐binding Small Molecules As Transcription Factor Inhibitorsmentioning

confidence: 99%

DNA‐Binding Small Molecules as Inhibitors of Transcription Factors

Leung

Chan

Pui‐Yan

et al. 2012

Medicinal Research Reviews

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Accumulating evidence implicating the role of aberrant transcription factor signaling in the pathogenesis of various human diseases such as cancer and inflammation has stimulated the development of small molecule ligands capable of targeting transcription factor activity and modulating gene expression. The use of DNA-binding small molecules to selectively inhibit transcription factor-DNA interactions represents one possible approach toward this goal. In this review, we summarize the development of DNA-binding small molecule inhibitors of transcription factors from 2004 to 2011, and their binding mode and therapeutic potential will be discussed.

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“…The fundamental forces dictating RNA-ligand interactions have been discussed elsewhere. 7,8 We note that the major groove of RNA duplexes, associated with a large negative electrostatic potential, can be rendered more accessible to small molecules by bulges and loops. This further exposes the hydrogen bonding face and the aromatic surfaces of the nucleobases for additional intermolecular interactions with potential binders.…”

Section: Introductionmentioning

confidence: 99%

Antibiotics that target protein synthesis

2010

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The key role of the bacterial ribosome makes it an important target for antibacterial agents. Indeed, a large number of clinically useful antibiotics target this complex translational ribonucleoprotein machinery. The majority of these compounds, mostly of natural origin, bind to one of the three key ribosomal sites: the decoding (or A-site) on the 30S, the peptidyl transferase center (PTC) on the 50S, and the peptide exit tunnel on the 50S. Antibiotics that bind the A-site, such as the aminoglycosides, interfere with codon recognition and translocation. Peptide bond formation is inhibited when small molecules like oxazolidinones bind at the PTC. Finally, macrolides tend to block the growth of the amino acid chain at the peptide exit tunnel. In this article, the major classes of antibiotics that target the bacterial ribosome are discussed and classified according to their respective target. Notably, most antibiotics solely interact with the RNA components of the bacterial ribosome. The surge seen in the appearance of resistant bacteria has not been met by a parallel development of effective and broad-spectrum new antibiotics, as evident by the introduction of only two novel classes of antibiotics, the oxazolidinones and lipopeptides, in the past decades. Nevertheless, this significant health threat has revitalized the search for new antibacterial agents and novel targets. High resolution structural data of many ribosome-bound antibiotics provide unprecedented insight into their molecular contacts and mode of action and inspire the design and synthesis of new candidate drugs that target this fascinating molecular machine.

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The Interactions of Small Molecules with DNA and RNA

Cited by 17 publications

References 128 publications

Challenges and current status of computational methods for docking small molecules to nucleic acids

Challenges and current status of computational methods for docking small molecules to nucleic acids

DNA‐Binding Small Molecules as Inhibitors of Transcription Factors

Antibiotics that target protein synthesis

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