Solid-phase synthesis of branched oligonucleotides containing a biologically relevant dCyd341 interstrand crosslink DNA lesion. Issue 10 (21st January 2020)

• Record Type: Journal Article
• Authors: Taverna Porro, Marisa L.; Saint-Pierre, Christine; Gasparutto, Didier; Ravanat, Jean-Luc
• Is Part Of: Organic & biomolecular chemistry. Volume 18:Issue 10(2020)
• Page Start: 1892
• Page End: 1899
• Publication Date: 2020-01-21
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c9ob01021a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Branched oligonucleotides containing a biologically relevant DNA lesion, involving an interstrand crosslink between a cytosine base on one strand and a ribose moiety on the opposite strand, were prepared in a single automated solid-phase synthesis. Abstract : Branched oligonucleotides containing a biologically relevant DNA lesion, dCyd341, which involves an interstrand crosslink between a cytosine base on one strand and a ribose moiety on the opposite strand, were prepared in a single automated solid-phase synthesis. For this, we first prepared the phosphoramidite analogue of dCyd341 bearing an orthogonal levulinyl protecting group. Then, following the synthesis of the first DNA strand containing dCyd341, the levulinic group was removed and the synthesis was then continued from the free base hydroxyl group at the branching point, using traditional phosphoramidites. The synthesized oligonucleotides were fully characterized by MALDI-TOF/MS and were enzymatically digested, and the presence of the lesion was confirmed by HPLC-MS/MS and the sequence was finally controlled upon exonuclease digestion followed by MALDI-TOF/MS analysis. The developed strategy was successfully employed for the preparation of several short linear and branched oligonucleotides containing the aforementioned lesion.