Beyond guanine quartets: Cation-induced formation of homogenous and chimeric DNA tetraplexes incorporating iso-guanine and guanine

Christopher Roberts, John C. Chaput, Christopher Switzer

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Background: iso-Guanine (iso-G) is the purine component of an isomeric Watson-Crick base pair that may have existed prebiotically. By comparing the abiotic molecular recognition properties of iso-G and its complement, iso-cytosine (iso-C), with those of genomic nucleotide bases, it may be possible to explain the exclusion of the iso-G-iso-C base pair from modem genomes. Whether a nucleobase forms quartets may have a key role in determining its functionality. Biotically, nucleic acid tetraplexes have been implicated in cellular functions; prebiotically, tetraplexes would probably interfere with replication. Recently, in vitro selection has yielded receptors and catalysts that incorporate G quartets. The versatility of these structures could be enhanced by expanding the range of bases that can form the quartet motif. Results: Native polyacrylamide gel electrophoresis of oligonucleotides bearing runs of iso-G provides strong support for tetraplex formation via cation-promoted DNA strand association. In particular, when strands of different lengths bearing the same iso-G tetrad recognition element were combined, five bands were observed after electrophoresis, corresponding to all possible heterotetraplexes with parallel strand alignment. An analogous experiment with a mixture of strands bearing iso-G or G tetrad recognition domains supports the existence of mixed iso-G/G tetraplexes with antiparallel strand alignment at chimeric junctions. iso-G tetraplex and quartet structure has also been probed by a photo-crosslinking experiment, ultra-violet spectroscopy and theoretical calculations. Conclusions: As iso-G and G both have a marked tendency to form tetraplexes, their tandem inclusion in genetic material may be problematic, leading to double-stranded DNA half composed of bases that have a tendency to auto-associate. The resulting density of 'selfish' bases could undermine Watson-Crick pair formation, especially in a prebiotic context devoid of enzymes. Nevertheless, the ability of iso-G to form mixed quartets with G may provide a basis for altering the properties of tetraplexes in the domain of artificial receptors or catalysts from in vitro selections.

Original languageEnglish (US)
Pages (from-to)899-908
Number of pages10
JournalChemistry and Biology
Volume4
Issue number12
DOIs
StatePublished - Dec 1997

Keywords

  • Ab initio theoretical
  • Guanine
  • Iso-guanine
  • Quartet
  • Tetraplex

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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