Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA

Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Scientific reports 2020-01, Vol.10 (1), p.1138, Article 1138
Hauptverfasser: Koseki, Jun, Konno, Masamitsu, Asai, Ayumu, Horie, Naohiro, Tsunekuni, Kenta, Kawamoto, Koichi, Obika, Satoshi, Doki, Yuichiro, Mori, Masaki, Ishii, Hideshi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 1
container_start_page 1138
container_title Scientific reports
container_volume 10
creator Koseki, Jun
Konno, Masamitsu
Asai, Ayumu
Horie, Naohiro
Tsunekuni, Kenta
Kawamoto, Koichi
Obika, Satoshi
Doki, Yuichiro
Mori, Masaki
Ishii, Hideshi
description Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH– π , lone pair (LP)– π , and π – π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.
doi_str_mv 10.1038/s41598-020-57899-7
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6981298</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2344544274</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-1262b118cc89c3fbe8eb2541d2a21a59766bf41046b02490db525ad5905f65183</originalsourceid><addsrcrecordid>eNp9UcFOHSEUJU2baqw_0EUzSdejcAdmYNPEWKtNTLuxawLMxYeZN7wCY3x_X55Prd2UDTf3nHvOhUPIR0ZPGO3kaeZMKNlSoK0YpFLt8IYcAuWihQ7g7av6gBznfEfrEaA4U-_JQceUpL0Uh2R7s8KYsARnpsbMZtpmzLUYG3zYYAprnEtF7s0URlNCnJvom7LCBr1HV3LjzJJxbOz2seunJaYwm1JbebG5hLJUhWYdx-Crx7PC1x9nH8g7b6aMx0_3Efn17eLm_Kq9_nn5_fzsunV84KVl0INlTDonleu8RYkWBGcjGGBGqKHvreeM8t5S4IqOVoAwo1BU-F4w2R2RL3vdzWLXOLq6TjKT3tS3mbTV0QT9LzKHlb6N97pXkoHaCXx-Ekjx94K56Lu4pPpVWUPHueAcBl5ZsGe5FHNO6F8cGNW7xPQ-MV0T04-J6aEOfXq928vIcz6V0O0JuULzLaa_3v-R_QNcVKPJ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2344544274</pqid></control><display><type>article</type><title>Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Koseki, Jun ; Konno, Masamitsu ; Asai, Ayumu ; Horie, Naohiro ; Tsunekuni, Kenta ; Kawamoto, Koichi ; Obika, Satoshi ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi</creator><creatorcontrib>Koseki, Jun ; Konno, Masamitsu ; Asai, Ayumu ; Horie, Naohiro ; Tsunekuni, Kenta ; Kawamoto, Koichi ; Obika, Satoshi ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi</creatorcontrib><description>Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH– π , lone pair (LP)– π , and π – π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-57899-7</identifier><identifier>PMID: 31980685</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>119/118 ; 5-Fluorouracil ; 631/57/2266 ; 639/705/1042 ; Adenine ; Adenine - chemistry ; Antimetabolites, Antineoplastic - chemistry ; Base Pairing ; Body temperature ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - drug effects ; DNA Damage ; Fluorouracil - chemistry ; Frontotemporal dementia ; Humanities and Social Sciences ; Hydrogen Bonding ; Incorporation ; Molecular Dynamics Simulation ; Molecular Structure ; multidisciplinary ; Nucleic Acid Conformation ; Nucleic acids ; Quantum Theory ; Science ; Science (multidisciplinary) ; Thermodynamics ; Trifluridine - chemistry</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.1138, Article 1138</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-1262b118cc89c3fbe8eb2541d2a21a59766bf41046b02490db525ad5905f65183</citedby><cites>FETCH-LOGICAL-c474t-1262b118cc89c3fbe8eb2541d2a21a59766bf41046b02490db525ad5905f65183</cites><orcidid>0000-0001-6960-2315 ; 0000-0002-6842-6812</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981298/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981298/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31980685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koseki, Jun</creatorcontrib><creatorcontrib>Konno, Masamitsu</creatorcontrib><creatorcontrib>Asai, Ayumu</creatorcontrib><creatorcontrib>Horie, Naohiro</creatorcontrib><creatorcontrib>Tsunekuni, Kenta</creatorcontrib><creatorcontrib>Kawamoto, Koichi</creatorcontrib><creatorcontrib>Obika, Satoshi</creatorcontrib><creatorcontrib>Doki, Yuichiro</creatorcontrib><creatorcontrib>Mori, Masaki</creatorcontrib><creatorcontrib>Ishii, Hideshi</creatorcontrib><title>Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH– π , lone pair (LP)– π , and π – π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.</description><subject>119/118</subject><subject>5-Fluorouracil</subject><subject>631/57/2266</subject><subject>639/705/1042</subject><subject>Adenine</subject><subject>Adenine - chemistry</subject><subject>Antimetabolites, Antineoplastic - chemistry</subject><subject>Base Pairing</subject><subject>Body temperature</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - drug effects</subject><subject>DNA Damage</subject><subject>Fluorouracil - chemistry</subject><subject>Frontotemporal dementia</subject><subject>Humanities and Social Sciences</subject><subject>Hydrogen Bonding</subject><subject>Incorporation</subject><subject>Molecular Dynamics Simulation</subject><subject>Molecular Structure</subject><subject>multidisciplinary</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleic acids</subject><subject>Quantum Theory</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Thermodynamics</subject><subject>Trifluridine - chemistry</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9UcFOHSEUJU2baqw_0EUzSdejcAdmYNPEWKtNTLuxawLMxYeZN7wCY3x_X55Prd2UDTf3nHvOhUPIR0ZPGO3kaeZMKNlSoK0YpFLt8IYcAuWihQ7g7av6gBznfEfrEaA4U-_JQceUpL0Uh2R7s8KYsARnpsbMZtpmzLUYG3zYYAprnEtF7s0URlNCnJvom7LCBr1HV3LjzJJxbOz2seunJaYwm1JbebG5hLJUhWYdx-Crx7PC1x9nH8g7b6aMx0_3Efn17eLm_Kq9_nn5_fzsunV84KVl0INlTDonleu8RYkWBGcjGGBGqKHvreeM8t5S4IqOVoAwo1BU-F4w2R2RL3vdzWLXOLq6TjKT3tS3mbTV0QT9LzKHlb6N97pXkoHaCXx-Ekjx94K56Lu4pPpVWUPHueAcBl5ZsGe5FHNO6F8cGNW7xPQ-MV0T04-J6aEOfXq928vIcz6V0O0JuULzLaa_3v-R_QNcVKPJ</recordid><startdate>20200124</startdate><enddate>20200124</enddate><creator>Koseki, Jun</creator><creator>Konno, Masamitsu</creator><creator>Asai, Ayumu</creator><creator>Horie, Naohiro</creator><creator>Tsunekuni, Kenta</creator><creator>Kawamoto, Koichi</creator><creator>Obika, Satoshi</creator><creator>Doki, Yuichiro</creator><creator>Mori, Masaki</creator><creator>Ishii, Hideshi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6960-2315</orcidid><orcidid>https://orcid.org/0000-0002-6842-6812</orcidid></search><sort><creationdate>20200124</creationdate><title>Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA</title><author>Koseki, Jun ; Konno, Masamitsu ; Asai, Ayumu ; Horie, Naohiro ; Tsunekuni, Kenta ; Kawamoto, Koichi ; Obika, Satoshi ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-1262b118cc89c3fbe8eb2541d2a21a59766bf41046b02490db525ad5905f65183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>119/118</topic><topic>5-Fluorouracil</topic><topic>631/57/2266</topic><topic>639/705/1042</topic><topic>Adenine</topic><topic>Adenine - chemistry</topic><topic>Antimetabolites, Antineoplastic - chemistry</topic><topic>Base Pairing</topic><topic>Body temperature</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>DNA - drug effects</topic><topic>DNA Damage</topic><topic>Fluorouracil - chemistry</topic><topic>Frontotemporal dementia</topic><topic>Humanities and Social Sciences</topic><topic>Hydrogen Bonding</topic><topic>Incorporation</topic><topic>Molecular Dynamics Simulation</topic><topic>Molecular Structure</topic><topic>multidisciplinary</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic acids</topic><topic>Quantum Theory</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Thermodynamics</topic><topic>Trifluridine - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koseki, Jun</creatorcontrib><creatorcontrib>Konno, Masamitsu</creatorcontrib><creatorcontrib>Asai, Ayumu</creatorcontrib><creatorcontrib>Horie, Naohiro</creatorcontrib><creatorcontrib>Tsunekuni, Kenta</creatorcontrib><creatorcontrib>Kawamoto, Koichi</creatorcontrib><creatorcontrib>Obika, Satoshi</creatorcontrib><creatorcontrib>Doki, Yuichiro</creatorcontrib><creatorcontrib>Mori, Masaki</creatorcontrib><creatorcontrib>Ishii, Hideshi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koseki, Jun</au><au>Konno, Masamitsu</au><au>Asai, Ayumu</au><au>Horie, Naohiro</au><au>Tsunekuni, Kenta</au><au>Kawamoto, Koichi</au><au>Obika, Satoshi</au><au>Doki, Yuichiro</au><au>Mori, Masaki</au><au>Ishii, Hideshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-24</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>1138</spage><pages>1138-</pages><artnum>1138</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH– π , lone pair (LP)– π , and π – π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31980685</pmid><doi>10.1038/s41598-020-57899-7</doi><orcidid>https://orcid.org/0000-0001-6960-2315</orcidid><orcidid>https://orcid.org/0000-0002-6842-6812</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2045-2322
ispartof Scientific reports, 2020-01, Vol.10 (1), p.1138, Article 1138
issn 2045-2322
2045-2322
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6981298
source MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects 119/118
5-Fluorouracil
631/57/2266
639/705/1042
Adenine
Adenine - chemistry
Antimetabolites, Antineoplastic - chemistry
Base Pairing
Body temperature
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - drug effects
DNA Damage
Fluorouracil - chemistry
Frontotemporal dementia
Humanities and Social Sciences
Hydrogen Bonding
Incorporation
Molecular Dynamics Simulation
Molecular Structure
multidisciplinary
Nucleic Acid Conformation
Nucleic acids
Quantum Theory
Science
Science (multidisciplinary)
Thermodynamics
Trifluridine - chemistry
title Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T09%3A58%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Theoretical%20analyses%20and%20experimental%20validation%20of%20the%20effects%20caused%20by%20the%20fluorinated%20substituent%20modification%20of%20DNA&rft.jtitle=Scientific%20reports&rft.au=Koseki,%20Jun&rft.date=2020-01-24&rft.volume=10&rft.issue=1&rft.spage=1138&rft.pages=1138-&rft.artnum=1138&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-57899-7&rft_dat=%3Cproquest_pubme%3E2344544274%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2344544274&rft_id=info:pmid/31980685&rfr_iscdi=true