editorial g-quadruplexes (gqu) · 2019. 7. 30. · editorial g-quadruplexes (gqu) shozebhaider ,1...

EditorialG-Quadruplexes (GQU)

Shozeb Haider 1 Gary N Parkinson1 and Thomas C Marsh2

1UCL School of Pharmacy University College London London UK2Department of Chemistry University of St Thomas St Paul MN USA

Correspondence should be addressed to Shozeb Haider shozebhaideruclacuk

Received 4 March 2018 Accepted 7 March 2018 Published 30 April 2018

Copyright copy 2018 Shozeb Haider et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The articles in this special edition provide a view of the com-plexity that guanine bases and their modifications present inboth lower and complex organisms and eukaryotic organ-isms Guanine nucleotides and guanine-rich nucleic acidshave a well-known propensity to self-associate into highlystable structures with a common structural motif of fourHoogsteen H-bonded coplanar guanines referred to as aG-quartet (aka G-tetrad) A relatively distinctive feature ofstacked G-quartets compared to Watson-Crick base pairedstructures is the presence of a coordination pocket that isoften occupied by a variety of physiological cations such asK+ NH

4

+ Ca2+ and Na+ as well as others such as Sr2+and Pb2+ Overall the stability and morphology of G-quartetstructures are influenced by a combination of intrinsic andexternal factors (eg sequence and coordinating cation) witha growing degree of predictability Evidence of the broaderrole G-quadruplexes play in information metabolism hasalso grown tremendously in the past decades giving uspotential therapeutic targets for cancer and similar diseasesFurthermore the key interactions that guanine makes havebeen used for their application as electrochemical biosensorsand development of nanoscale devices

Two articles are presented by V Viglasky et al Inone article they scan the human and simian immunodefi-ciency provirus genome for putative G-quadruplex formingsequences They rationalize that targeting the G-quadru-plexes in HIV offers an attractive therapeutic target whichwould be of particular use in the development of novelantiviral therapiesThe analysis of G-rich regions can provideresearchers with a path to find specific targets that could beof interest for specific types of virus In the other articlethey trace the effect of modifications in telomeric sequencesin Tetrahymena and human repeats The human telomeric

and protozoan telomeric sequences differ only in one purinebase (TTAGGG to TTGGGG) They go on to demonstratethat while the substitution does not affect the formation ofG-quadruplexes it does result in an alteration of topologyThe results also show that the stability of the substitutedderivatives increased in sequences with greater number ofsubstitutions This observation is somewhat analogous to thephenomenon observed in human telomeric sequences wherethe same TTAGGG sequence can adopt six different types oftopologies depending upon the chemical environment

The importance of G-quadruplex function can be empha-sized just based on the number of proteins that are beingreported that have an association with them While G-quadruplexes are being touted as potential drug targetsand small molecule compounds are being developed stillvery little is known about how these multistranded nucleicacids structures interact with proteins The review by S AMcKenna et al focuses on the recognition and comparisonof G-quadruplexes by proteins and small peptides mainlytaking into account the X-ray crystallographic and NMRstructures as well as biochemical investigations of bindingspecificity These structural features can be used to study andrationally designmolecules that target protein-G-quadruplexinteractions

In another article J Sagi reviews the structural stabil-ity of natural base lesion and synthetic nucleotides Thecomprehensive review on the thermodynamic stability ofthe modified G-quadruplex folds and the stereochemicalpreferences of more than 70 synthetic and natural derivativesof nucleotides substituting for the natural ones determinethe stability and their conformation The stability of thenucleotide analogs depends on the glycosidic bond confor-mation their position of occurrence and the quadruplex

HindawiJournal of Nucleic AcidsVolume 2018 Article ID 1079191 2 pageshttpsdoiorg10115520181079191

2 Journal of Nucleic Acids

fold Base modifications hold extreme importance in epi-genetic studies An insight into the thermodynamics of G-quadruplex structural stability can be useful in engineeringa stable G-quadruplex topology and in exploring the actionof base modifications on G-quadruplex architectures both invitro and in vivo

In another article G Wu et al explore a five-decade oldquestionwhat is the handedness of 51015840-GMPhelical structureThey report using NMR and IR spectroscopy the structuraldetails of the helix which contains 15 nucleotides per 4 turnsand only C3rsquo-endo sugar puckering The switch in pH from 8to 5 results in the helix being devoid of Na+ ions which is insharp contrast to the 51015840-GMP helix formed at pH 8 where thecentral channel is filled with Na+ ions

In another article A M Oliveira-Brett et al reviewthe recent advances in the applications of G-quadruplexesas biosensors G-quadruplex electrochemical biosensorshave received particular attention since the electrochemicalresponse is particularly sensitive to the DNA structuralchanges from a single-stranded double-stranded or hairpininto a G-quadruplex configuration The development of anincreasednumber ofG-quadruplex aptamers which combinethe G-quadruplex stiffness and self-assembling versatilitywith the aptamer high specificity of binding to a varietyof molecular targets allowed the construction of biosensorswith increased selectivity and sensitivityThe electrochemicalcharacterization design and applications of G-quadruplexelectrochemical biosensors in the evaluation of metal ionsG-quadruplex ligands and other small organic moleculesproteins and cells are reviewed The electrochemical andatomic force microscopy characterization of G-quadruplexesis presented Different G-quadruplex electrochemical biosen-sors design strategies based on the DNA folding into a G-quadruplex the use of G-quadruplex aptamers or the use ofG-quadruplex DNAzymes are discussed

Acknowledgments

Finally the editors of this issue would like to thank all theauthors and referees involved in the peer-reviewing process

Shozeb HaiderGary N ParkinsonThomas C Marsh

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fold Base modifications hold extreme importance in epi-genetic studies An insight into the thermodynamics of G-quadruplex structural stability can be useful in engineeringa stable G-quadruplex topology and in exploring the actionof base modifications on G-quadruplex architectures both invitro and in vivo

In another article G Wu et al explore a five-decade oldquestionwhat is the handedness of 51015840-GMPhelical structureThey report using NMR and IR spectroscopy the structuraldetails of the helix which contains 15 nucleotides per 4 turnsand only C3rsquo-endo sugar puckering The switch in pH from 8to 5 results in the helix being devoid of Na+ ions which is insharp contrast to the 51015840-GMP helix formed at pH 8 where thecentral channel is filled with Na+ ions

In another article A M Oliveira-Brett et al reviewthe recent advances in the applications of G-quadruplexesas biosensors G-quadruplex electrochemical biosensorshave received particular attention since the electrochemicalresponse is particularly sensitive to the DNA structuralchanges from a single-stranded double-stranded or hairpininto a G-quadruplex configuration The development of anincreasednumber ofG-quadruplex aptamers which combinethe G-quadruplex stiffness and self-assembling versatilitywith the aptamer high specificity of binding to a varietyof molecular targets allowed the construction of biosensorswith increased selectivity and sensitivityThe electrochemicalcharacterization design and applications of G-quadruplexelectrochemical biosensors in the evaluation of metal ionsG-quadruplex ligands and other small organic moleculesproteins and cells are reviewed The electrochemical andatomic force microscopy characterization of G-quadruplexesis presented Different G-quadruplex electrochemical biosen-sors design strategies based on the DNA folding into a G-quadruplex the use of G-quadruplex aptamers or the use ofG-quadruplex DNAzymes are discussed

Acknowledgments

Finally the editors of this issue would like to thank all theauthors and referees involved in the peer-reviewing process

Shozeb HaiderGary N ParkinsonThomas C Marsh



Volume 2018

Zoology











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Advances in




Enzyme Research





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