Enhanced RNA binding of dimerized aminoglycosides.


:Aminoglycoside antibiotics have recently emerged as an intriguing family of RNA binding molecules and they became leading structures for the design of novel RNA ligands. The demystification of the aminoglycoside-RNA recognition phenomenon is required for the development of superior binders. To explore the existence of multiple binding sites in a large RNA molecule, we have synthesized covalently linked symmetrical and nonsymmetrical dimeric aminoglycosides. These unnatural derivatives were compared to their natural "monomeric" counterparts in their ability to inhibit the Tetrahymena ribozyme. The dimeric aminoglycosides inhibit ribozyme function 20 to 1.2 x 10(3) fold more effectively than their natural parent compounds. The inhibition curves of dimeric aminoglycosides have characteristic shapes suggesting the presence of at least two high affinity-binding sites within the ribozyme's three-dimensional fold. The interaction of a dimeric aminoglycoside with two complementary sites of the RNA molecule is proposed. This binding motif may have implications on the development of new drugs targeting pivotal RNA molecules of bacterial and viral pathogens.


Bioorg Med Chem


Michael K,Wang H,Tor Y




Has Abstract


1999-07-01 00:00:00














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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Shin SY,Yoon H,Hwang D,Ahn S,Kim DW,Koh D,Lee YH,Lim Y

    更新日期:2013-11-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Azhdarinia A,Wilganowski N,Robinson H,Ghosh P,Kwon S,Lazard ZW,Davis AR,Olmsted-Davis E,Sevick-Muraca EM

    更新日期:2011-06-15 00:00:00

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    abstract::1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analog...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Thakkar SS,Thakor P,Doshi H,Ray A

    更新日期:2017-08-01 00:00:00