Modified Nucleic Acids

280 Pages·2016·11.7 MB·English

by  Kazuhiko Nakatani

Nucleic Acids and Molecular Biology 31
Kazuhiko Nakatani
Yitzhak Tor Editors
Modifi ed
Nucleic
Acids
Nucleic Acids and Molecular Biology
Volume 31
Serieseditor
JanuszM.Bujinicki
InternationalInstituteofMolecular
andCellBiology
LaboratoryofBioinformaticsand
ProteinEngineering
Trojdena4
02-109Warsaw
Poland
More information about this series at http://www.springer.com/series/881
Kazuhiko Nakatani (cid:129) Yitzhak Tor
Editors
Modified Nucleic Acids
Editors
KazuhikoNakatani YitzhakTor
TheInstituteofScientificandIndustrial UniversityofCalifornia,SanDiego
Research LaJolla
OsakaUniversity California
Ibaraki,Osaka USA
Japan
ISSN0933-1891 ISSN1869-2486 (electronic)
NucleicAcidsandMolecularBiology
ISBN978-3-319-27109-5 ISBN978-3-319-27111-8 (eBook)
DOI10.1007/978-3-319-27111-8
LibraryofCongressControlNumber:2015960936
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Preface
Modifiednucleosides,nucleotides,andoligonucleotideshavebecomeamainstayof
modernscience.Usedasbiochemicalandbiophysicaltools,aswellasactualdrugs
andkeycomponentofdiscoveryassays,onecannotbutappreciatetheimpactsuch
synthetic analogs have had on chemistry, biology, and medicine over the past
several decades. With this backdrop in mind, we have put together this edited
volumetohonorProfessorIsaoSaitoandcelebratehisrecentretirement,whichalso
provided us with the opportunity to share some of his contributions with the
community.
For those of us who operate in the exciting field of modified nucleic acids,
Professor Saito needs no introduction. For the benefit of the younger readers, we
verybrieflyhighlightsomeofhisinterests.Trainedasasyntheticchemist,Profes-
sorSaitoturnedhisattentiontobiologicalproblemsearlyinhiscareer,asthefield
focusing on the chemical biology of nucleic acids started emerging. While on the
faculty at Kyoto University, he has made numerous contributions to the develop-
ment of photochemical transformations, including a light-mediated cross-linking
reaction ofDNA.Ashisinterestsinelectrontransferreactions,photophysics,and
photobiology evolved, he combined his synthetic skills to develop new modified
nucleosides as probes. Most notable for the community interested in developing
fluorescent analogs of biomolecular building blocks, his work on base-
discriminating fluorescent (BDF) nucleosides, which has been advanced while on
thefacultyatNihonUniversityoverthepastdozenyears,standsoutasithasserved
asinspirationforresearchgroupsaroundtheworld.
Appropriately,thefirstchapterinourcollection,byTordiscussesthesynthesis
andpropertiesofemissive5-modifieduridineanalogs,anareaextensivelyexplored
by the Saito group. Perhaps complementary to this pyrimidine-centric discussion,
the following chapter by Saito presents emissive fluorescent purine analogs.
Various modifications are discussed, with attention to historically important con-
tributions.Stayingwithinthegeneralareaoffluorescentoligonucleotides,Okamoto
then discusses the utility on thiazole orange, when tethered to nucleic acid, as a
probeformonitoringnucleicacid-basedprocessesbothinvitroandinvivo.Along
v
vi Preface
related themes, Wagenknecht elaborates on his approaches to emissive nucleic
acids,labeledwithcyanine-styrylfluorophores.Inparticular,thechapterhighlights
his “DNA/RNA Traffic Lights,” where the combination of thiazole orange and
thiazole red facilitates the development of novel multicolor probes. In a similar
fashion and relying on the double helical architecture to dictate the interactions
betweenchromophores,Yamanadiscusseshismultichromophoreassemblies.Par-
ticularlyintriguingaretheuniquephotophysicalfeaturesemergingandthesignif-
icantdifferencesobservedbetweenDNAandRNAduplexes.
Enzymaticapproachestothepreparationofmodifiednucleicacidarediscussed
by Hocek. In particular, effective approaches for the synthesis of modified tri-
phosphates are highlighted. When recognized by polymerases, such a building
block can provide an effective pathway for assembling modified nucleic acids.
Once incorporated, modified nucleosides and nucleoside surrogates can serve
diversepurposes.Inthefollowingchapter,Fujimotodiscussestheutilityofcross-
linking reactions. The formation of stable adducts can then be exploited for
chemical,biological,aswellasnanotechnologicalapplications.
While the majority of chapters in this book discuss photochemical and
photophysical processesinnucleicacids,Sigurdssontakesauniqueapproach and
exploitstheutilityofelectronparamagneticresonance(EPR)spectroscopytostudy
nucleicacidstructureanddynamics.Whilethereadouttoolisclearlydistinct,this
approachalsoreliesontheincorporationofmodified nucleosidesintooligonucle-
otides, albeit decorated with spin labels rather than with photoactive or emissive
chromophores.ThechapterprovidesanexcellentintroductiontoEPRspectroscopy
and highlights a wide spectrum of stable free-radical-containing nucleoside
analogs.
Yet another distinct approach is taken by Nakatani, who relies on noncovalent
binding of low MW ligands to a DNA scaffold to endow the resulting assemblies
with novel properties. Specifically, ligands with high affinity to mismatched or
unpairedsites(coinedMBL),containinga1,8-naphthyridinecore,areshowntobe
versatile building blocks for diverse applications, ranging from nanostructure
assembly to monitoring processes such as PCR. Another approach for the
noncovalent assembly of higher structures is presented by Obika, who utilizes
synthetictriplex-formingoligonucleotides(TFO).Restrictingtheriboseconforma-
tion by covalently bridging the 20 and 40 positions is shown to be a promising
solutiontosomeofthelong-standinglimitationswhichhaveimpactedthisfield.
Keeping with the theme of modified nucleosides and their utility, Sasaki dis-
cusses several useful approaches for nucleic acid modification and for sensing
damaged nucleotides. Specifically, modified nucleosides capable of forming
sequence-specific cross-links are presented, and examples for their utility in the
context of both double-stranded and other folds (e.g., triplexes, i-motifs) are
discussed.Furthermore,amethodfordetecting8-oxoguanosine,adamagednucle-
oside, which serves as a biomarker for cellular oxidative stress, is presented.
Finally, Hirao discusses his elegant approach for the design of unnatural base
pairs, which are orthogonal to the native Watson–Crick ones. Such expanded
genetic alphabets, which can be replicated and transcribed with high fidelity,
Preface vii
have found intriguing biotechnological applications, including the generation of
modifiedaptamersfortargetingspecificproteinsandcells.
Ithasbeenourpleasureeditingthesecontributionsandassemblingthisvolume
inhonorofProfessorSaito.Wewishhimjoyinpursuinghisdiversepassionsashe
retires from academia. His special take on bioorganic chemistry and chemical
biology will certainly last, as the individuals he had trained are now populating
illustriousacademicinstitutionsandpursuingtheirownindependentinvestigations,
undoubtedly inspired by his pioneering work. We hope the reader, including
studentsandyounginvestigators,alsofindinspirationinlearningaboutthecontri-
butions madebymoreestablishedinvestigatorsandfeel motivatedtobeboldand
creativelyexploretheirownuniquemultidisciplinarydirections.
Osaka,Japan KazuhikoNakatani
LaJolla,CA YitzhakTor
August2015
ThiSisaFMBlankPage
Contents
1 Emissive5-SubstitutedUridineAnalogues. . . . . . . . . . . . . . . . . . . 1
AndreaFin,AlexanderR.Rovira,PatrycjaA.Hopkins,andYitzhakTor
2 FluorescentPurineNucleosidesandTheirApplications. . . . . . . . . 27
YoshioSaito,AzusaSuzuki,andIsaoSaito
3 ThiazoleOrange-TetheredNucleicAcidsandECHOProbes
forFluorometricDetectionofNucleicAcids. . . . . . . . . . . . . . . . . . 63
AkimitsuOkamoto
4 SyntheticWavelength-ShiftingFluorescentProbesofNucleic
Acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
ChristianSchwechheimer,MarcusMerkel,PeggyR.Bohla¨nder,
andHans-AchimWagenknecht
5 DNA-AssistedMultichromophoreAssembly. . . . . . . . . . . . . . . . . . 101
TadaoTakada,MitsunobuNakamura,andKazushigeYamana
6 PolymeraseSynthesisofBase-ModifiedDNA. . . . . . . . . . . . . . . . . 123
JitkaDadova´,HanaCahova´,andMichalHocek
7 Photo-Cross-LinkingReactioninNucleicAcids:Chemistry
andApplications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
TakashiSakamotoandKenzoFujimoto
8 Site-DirectedSpinLabelingforEPRStudiesofNucleicAcids. . . . 159
SandipA.ShelkeandSnorriTh.Sigurdsson
9 Non-covalentModificationofDouble-StrandedDNA
attheMismatchandBulgedSite. . . . . . . . . . . . . . . . . . . . . . . . . . 189
ChikaraDohnoandKazuhikoNakatani
10 20,40-BridgedNucleicAcidsforTargeting
Double-StrandedDNA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
YoshiyukiHariandSatoshiObika
ix