Evaluation of the Base‐Pairing Properties of 5‐(5‐Indolylethynyl) and 5‐(5‐Indolyl)‐2′‐deoxyuridine Modified Triplex and Duplex. Issue 32 (27th August 2020)

• Record Type: Journal Article
• Authors: Fatthalla, Maha I.; Pedersen, Erik B.
• Is Part Of: ChemistrySelect. Volume 5:Issue 32(2020)
• Page Start: 10067
• Page End: 10071
• Publication Date: 2020-08-27
• Subjects: CSO oxidizer -- deoxyuridine -- indole -- nucleobase iodination -- parallel triplex; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202002174
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Indole was conjugated to deoxyuridine either directly or via ethynyl linkage to synthesize two new DNA monomers. Due to the high reactivity of indole toward electrophilic substitution reactions, unwanted iodination was observed during the oxidation step with iodine oxidizer in automated DNA synthesizer leading to an additional oligonucleotide having extra 126 mass unit beside the desired oligonucleotide. On the other hand, using CSO oxidizer ensured the formation of the wanted oligonucleotide. Oligonucleotide synthesis was confirmed by MALDI‐TOF‐MS analysis. Polypyrimidine strands containing non‐iodinated indole nucleoside were able to form parallel triplexes, antiparallel RNA and DNA duplexes. The thermal denaturation experiments showed higher triplex stabilization for 5‐(5‐indolylethynyl)‐2′‐deoxyuridine over 5‐(5‐indolyl)‐2′‐deoxyuridine as the triple bond allows twisting to put the indole into a proper position within the triplex encouraging better π‐π stacking. Abstract : Free (NH)‐indole containing nucleosides were synthesized and linked to deoxyuridine either directly or via ethynyl linkage. The free NH accelerates unprecedented iodination reaction of indole during DNA synthesis using iodine oxidizer, the problem was solved by using CSO‐oxidizer. The ability to form stable triplexes and duplexes was evaluated to show the enhanced ability of ethynyl nucleoside to stabilize parallel triplexes, antiparallel RNA and DNA duplexes compared to truncated nucleoside. Moreover, a great destabilization was observed due to the iodinated nucleoside.