Synthesis and fluorescence study of 7-azaindole in DNA oligonucleotides replacing a purine base

Abstract

The fluorescence spectroscopy of 7-azaindole ( 7a In) incorporated in DNA oligonucleotides is investigated. Incorporation of 7a In into DNA oligonucleotides is accomplished through standard solid-phase phosphoramidite chemistry. Fluorescence emission of the 7a In chromophore shifts slightly to the red (from 386 nm to 388 nm) upon glycosylation at the N − 1 position, but its relative fluorescence quantum yield increases 23 times, from 0.023 to 0.53. Upon incorporation into DNA, the fluorescence emission of 7a In is greatly quenched with fluorescence quantum yields of 0.020 and 0.016 in single and double strand DNA, respectively. The fluorescence emission for 7a In in DNA oligonucleotides shifts to the blue with an emission maximum at 379 nm. Both the strong fluorescence quenching and the blue shift of the emission spectrum signify that 7a In is stacked with neighboring DNA bases in both single and double strand DNA. As the duplex DNA melts due to temperature increase, the fluorescence of the 7a In chromophore increases, indicating the transition from the less fluorescent duplex DNA to the more fluorescent single strand DNA. Since this fluorescent 7a In is a structural analog of purine, its fluorescence property may be utilized as a probe for studying nucleic acid structure and dynamics.

Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes

“…This effect is known for compounds covalently binding to ctDNA (including cisplatin ) [47], as well as for the substances intercalating into the structure of DNA (including free 7-azaindoles) [48–49]. The Stern-Volmer and apparent binding constants for complexes 6 ( K SV = 7.4 × 10 3 M –1 , K app = 7.8 × 10 4 M –1 ) and 8 ( K SV = 1.4 × 10 4 M –1 , K app = 1.2 × 10 5 M –1 ), were higher than those for cisplatin ( K SV = 4.7 × 10 3 M –1 , K app = 4.8 × 10 4 M –1 ) and showed on moderate binding affinity of complexes 6 and 8 to the ctDNA (Fig 5).…”

Excited-State Proton Transfer and Phototautomerism in Nucleobase and Nucleoside Analogs: A Mini-Review

“…[37] Both experimental and theoretical studies on 7-azaindole phototautomerism are ongoing in recent years. [41][42][43] The 7-azaindole itself is rather distantly related to natural nucleobases and therefore was rarely utilized in biophysical applications using fluorescence, [44,45] however, its amino-acid derivative, 7-azatryptophan, has been used extensively in the protein research. [46,47] The 1,N 6 -Ethenoadenosine Puzzle: What Is pK * of the Compound?…”

Universal Base Analogues and their Applications to Biotechnology

“…In the case of the triazolopyrimidines, the fluorescent properties were dependent upon the glycosylation position, with the N2-regioisomer (35) exhibiting the best fluorescent profile for use in hybridization probes [39]. 7-Azaindole (36) is another analogue that may be used as a fluorescent universal base analogue in hybridization probes [68], and Kool and coworkers have described a number of non-discriminatory fluorescent base analogues [69,70].…”