Your browser version may not work well with NCBI's Web applications. More information here...
1: ACS Chem Biol. 2007 Nov 20;2(11):745-54. Epub 2007 Nov 2.
Related Articles, Links
Click here to read Click here to read
A small molecule microarray platform to select RNA internal loop-ligand interactions.

Childs-Disney JL, Wu M, Pushechnikov A, Aminova O, Disney MD.

Department of Chemistry and Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, 657 Natural Sciences Complex, Buffalo, New York 14260, USA.

Herein, we report the development of a microarray platform to select RNA motif-ligand interactions that allows simultaneous screening of both RNA and chemical space. We used this platform to identify the RNA internal loops that bind 6'- N-5-hexynoate kanamycin A ( 1). Selected internal loops that bind 1 were studied in detail and commonly display an adenine across from a cytosine independent of the size of the loop. Additional preferences are also observed. For 3 x 3 nucleotide loops, there is a preference for purines, and for 2 x 2 nucleotide loops there is a preference for pyrimidines neighbored by an adenine across from a cytosine. This technique has several advantageous features for selecting RNA motif-ligand interactions: (1) higher affinity RNA motif-ligand interactions are identified by harvesting bound RNAs from lower ligand loadings; (2) bound RNAs are harvested from the array via gel extraction, mitigating kinetic biases in selections; and (3) multiple selections are completed on a single array surface. To further demonstrate that multiple selections can be completed in parallel on the same array surface, we selected the RNA internal loops from a 4096-member RNA internal loop library that bound a four-member aminoglycoside library. These experiments probed 16,384 (4 aminoglycoside x 4096-member RNA library) interactions in a single experiment. These studies allow for parallel screening of both chemical and RNA space to improve our understanding of RNA-ligand interactions. This information may facilitate the rational and modular design of small molecules targeting RNA.

Publication Types:
PMID: 17975888 [PubMed - indexed for MEDLINE]