کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1365102 | 981552 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Molecular probes of DNA bulges: Functional assay and spectroscopic analysis Molecular probes of DNA bulges: Functional assay and spectroscopic analysis](/preview/png/1365102.png)
Bulged structures in DNA and RNA have been linked to biomolecular processes involved in numerous diseases, thus probes with affinity for these nucleic acid targets would be of considerable utility to chemical biologists. Herein, we report guided chemical synthesis of small molecules capable of binding to DNA bulges by virtue of their unique (spirocyclic) geometry. The agents, modeled on a natural product congener, show pronounced selectivity for specific bulged motifs and are able to enhance slipped DNA synthesis, a hallmark functional assay of bulge binding. Significantly, bulge-agent complexes demonstrate characteristic fluorescent signatures depending on bulge and flanking sequence in the oligo. It is anticipated that these signature patterns can be harnessed as molecular probes of bulged hotspots in DNA and RNA.
A mimic of the natural product derived DNA bulge-binding agent NCSi-gb was prepared from an accessible compound using an α-fucosylation strategy. The congener shows pronounced affinity for two-base DNA bulges and is active in a functional DNA slippage assay. Fluorescence patterns induced between the agent and synthetic oligos suggest fingerprinting assays may be developed for the detection of bulged sites in DNA.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 2, 15 January 2007, Pages 784–790