Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer
Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most domi...
Gespeichert in:
Veröffentlicht in: | Biopolymers 2009-04, Vol.91 (4), p.256-264 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 264 |
---|---|
container_issue | 4 |
container_start_page | 256 |
container_title | Biopolymers |
container_volume | 91 |
creator | Mo, Jingjie Todd, Gabrielle C. Håkansson, Kristina |
description | Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most dominant nucleic acid secondary structure is the hairpin, formed by intrastrand hydrogen bonding between complementary nucleobases. We have previously applied gas‐phase hydrogen/deuterium exchange (HDX) with mass spectrometry detection to show that anionic DNA duplexes have lower HDX rates than their constituent monomers, indicating that hydrogen bonding can shield hydrogens from exchanging with the bath gas D2S. The same HDX assay is applied here to investigate nucleic acid hairpin structure. Variations in hairpin solution‐phase stabilities are achieved by changing their loop size, stem length, and stem composition (ratio of G/C and A/T(U) base pairs in the stem). These differences can be carried into the gas phase because electrospray ionization is a gentle ionization method that is able to preserve noncovalent interactions. Observed gas‐phase HDX rates of these hairpins are consistent with their relative solution‐phase stabilities as predicted by MFold, i.e., less stable nucleic acid hairpins exchange faster than more stable hairpins. To our knowledge, the presented experiments demonstrate for the first time that gas‐phase HDX may be used to characterize nucleic acid higher order structure and the results suggest that the relative stabilities of nucleic acid hairpins in the gaseous phase are correlated with those in solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 256–264, 2009.
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com |
doi_str_mv | 10.1002/bip.21134 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66882788</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66882788</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4274-34cdf9d61f61dbefb88facc4fe798cc741c3596f88828b7eefd9f9a6f9fddedb3</originalsourceid><addsrcrecordid>eNqFkc1u1DAURi0EokNhwQsgr5BYpGPHjmMvYUo7gyqoSlGXlmNfTwz5q52ITp--KTPACrHx3ZzveHEQek3JCSUkX1ZhOMkpZfwJWlCiyozkMn-KFoQQkbEiL47Qi5S-E8I5o-Q5OqKKckILsUD3q9pEY0eI4d6Moe9w73E32QaCxcYGh-uwrSHiPrr5TWOc7DhFwNUOb03KhtokwOvlKYY7W5tuCzh02ODbybg4DX0D2dl1tlld4dakhNMAdox9C_OHL9Ezb5oErw73GH07-3i9WmcXX843q_cXmeV5yTPGrfPKCeoFdRX4SkpvrOUeSiWtLTm1rFDCSylzWZUA3imvjPDKOweuYsfo7d47xP52gjTqNiQLTWM66KekhZiXpZT_BRkjSnEhZvDdHrSxTymC10MMrYk7TYl-LKLnIvpXkZl9c5BOVQvuL3lIMAPLPfAzNLD7t0l_2Fz-Vmb7RUgj3P1ZmPhDi5KVhb75fK7F1_XV5acboRV7AH2Apqc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>33099466</pqid></control><display><type>article</type><title>Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer</title><source>MEDLINE</source><source>Wiley Blackwell Journals</source><creator>Mo, Jingjie ; Todd, Gabrielle C. ; Håkansson, Kristina</creator><creatorcontrib>Mo, Jingjie ; Todd, Gabrielle C. ; Håkansson, Kristina</creatorcontrib><description>Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most dominant nucleic acid secondary structure is the hairpin, formed by intrastrand hydrogen bonding between complementary nucleobases. We have previously applied gas‐phase hydrogen/deuterium exchange (HDX) with mass spectrometry detection to show that anionic DNA duplexes have lower HDX rates than their constituent monomers, indicating that hydrogen bonding can shield hydrogens from exchanging with the bath gas D2S. The same HDX assay is applied here to investigate nucleic acid hairpin structure. Variations in hairpin solution‐phase stabilities are achieved by changing their loop size, stem length, and stem composition (ratio of G/C and A/T(U) base pairs in the stem). These differences can be carried into the gas phase because electrospray ionization is a gentle ionization method that is able to preserve noncovalent interactions. Observed gas‐phase HDX rates of these hairpins are consistent with their relative solution‐phase stabilities as predicted by MFold, i.e., less stable nucleic acid hairpins exchange faster than more stable hairpins. To our knowledge, the presented experiments demonstrate for the first time that gas‐phase HDX may be used to characterize nucleic acid higher order structure and the results suggest that the relative stabilities of nucleic acid hairpins in the gaseous phase are correlated with those in solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 256–264, 2009.
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com</description><identifier>ISSN: 0006-3525</identifier><identifier>EISSN: 1097-0282</identifier><identifier>DOI: 10.1002/bip.21134</identifier><identifier>PMID: 19140156</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Base Sequence ; Deuterium Exchange Measurement ; Gases - chemistry ; hydrogen exchange ; Mass Spectrometry ; Nucleic Acid Conformation ; nucleic acid structure ; Nucleic Acids - chemistry ; Solutions ; Solvents ; Spectroscopy, Fourier Transform Infrared</subject><ispartof>Biopolymers, 2009-04, Vol.91 (4), p.256-264</ispartof><rights>Copyright © 2009 Wiley Periodicals, Inc.</rights><rights>2008 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4274-34cdf9d61f61dbefb88facc4fe798cc741c3596f88828b7eefd9f9a6f9fddedb3</citedby><cites>FETCH-LOGICAL-c4274-34cdf9d61f61dbefb88facc4fe798cc741c3596f88828b7eefd9f9a6f9fddedb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbip.21134$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbip.21134$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19140156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mo, Jingjie</creatorcontrib><creatorcontrib>Todd, Gabrielle C.</creatorcontrib><creatorcontrib>Håkansson, Kristina</creatorcontrib><title>Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer</title><title>Biopolymers</title><addtitle>Biopolymers</addtitle><description>Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most dominant nucleic acid secondary structure is the hairpin, formed by intrastrand hydrogen bonding between complementary nucleobases. We have previously applied gas‐phase hydrogen/deuterium exchange (HDX) with mass spectrometry detection to show that anionic DNA duplexes have lower HDX rates than their constituent monomers, indicating that hydrogen bonding can shield hydrogens from exchanging with the bath gas D2S. The same HDX assay is applied here to investigate nucleic acid hairpin structure. Variations in hairpin solution‐phase stabilities are achieved by changing their loop size, stem length, and stem composition (ratio of G/C and A/T(U) base pairs in the stem). These differences can be carried into the gas phase because electrospray ionization is a gentle ionization method that is able to preserve noncovalent interactions. Observed gas‐phase HDX rates of these hairpins are consistent with their relative solution‐phase stabilities as predicted by MFold, i.e., less stable nucleic acid hairpins exchange faster than more stable hairpins. To our knowledge, the presented experiments demonstrate for the first time that gas‐phase HDX may be used to characterize nucleic acid higher order structure and the results suggest that the relative stabilities of nucleic acid hairpins in the gaseous phase are correlated with those in solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 256–264, 2009.
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com</description><subject>Base Sequence</subject><subject>Deuterium Exchange Measurement</subject><subject>Gases - chemistry</subject><subject>hydrogen exchange</subject><subject>Mass Spectrometry</subject><subject>Nucleic Acid Conformation</subject><subject>nucleic acid structure</subject><subject>Nucleic Acids - chemistry</subject><subject>Solutions</subject><subject>Solvents</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><issn>0006-3525</issn><issn>1097-0282</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAURi0EokNhwQsgr5BYpGPHjmMvYUo7gyqoSlGXlmNfTwz5q52ITp--KTPACrHx3ZzveHEQek3JCSUkX1ZhOMkpZfwJWlCiyozkMn-KFoQQkbEiL47Qi5S-E8I5o-Q5OqKKckILsUD3q9pEY0eI4d6Moe9w73E32QaCxcYGh-uwrSHiPrr5TWOc7DhFwNUOb03KhtokwOvlKYY7W5tuCzh02ODbybg4DX0D2dl1tlld4dakhNMAdox9C_OHL9Ezb5oErw73GH07-3i9WmcXX843q_cXmeV5yTPGrfPKCeoFdRX4SkpvrOUeSiWtLTm1rFDCSylzWZUA3imvjPDKOweuYsfo7d47xP52gjTqNiQLTWM66KekhZiXpZT_BRkjSnEhZvDdHrSxTymC10MMrYk7TYl-LKLnIvpXkZl9c5BOVQvuL3lIMAPLPfAzNLD7t0l_2Fz-Vmb7RUgj3P1ZmPhDi5KVhb75fK7F1_XV5acboRV7AH2Apqc</recordid><startdate>200904</startdate><enddate>200904</enddate><creator>Mo, Jingjie</creator><creator>Todd, Gabrielle C.</creator><creator>Håkansson, Kristina</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7U5</scope><scope>8FD</scope><scope>L7M</scope><scope>7X8</scope></search><sort><creationdate>200904</creationdate><title>Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer</title><author>Mo, Jingjie ; Todd, Gabrielle C. ; Håkansson, Kristina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4274-34cdf9d61f61dbefb88facc4fe798cc741c3596f88828b7eefd9f9a6f9fddedb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Base Sequence</topic><topic>Deuterium Exchange Measurement</topic><topic>Gases - chemistry</topic><topic>hydrogen exchange</topic><topic>Mass Spectrometry</topic><topic>Nucleic Acid Conformation</topic><topic>nucleic acid structure</topic><topic>Nucleic Acids - chemistry</topic><topic>Solutions</topic><topic>Solvents</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mo, Jingjie</creatorcontrib><creatorcontrib>Todd, Gabrielle C.</creatorcontrib><creatorcontrib>Håkansson, Kristina</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Biopolymers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mo, Jingjie</au><au>Todd, Gabrielle C.</au><au>Håkansson, Kristina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer</atitle><jtitle>Biopolymers</jtitle><addtitle>Biopolymers</addtitle><date>2009-04</date><risdate>2009</risdate><volume>91</volume><issue>4</issue><spage>256</spage><epage>264</epage><pages>256-264</pages><issn>0006-3525</issn><eissn>1097-0282</eissn><abstract>Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most dominant nucleic acid secondary structure is the hairpin, formed by intrastrand hydrogen bonding between complementary nucleobases. We have previously applied gas‐phase hydrogen/deuterium exchange (HDX) with mass spectrometry detection to show that anionic DNA duplexes have lower HDX rates than their constituent monomers, indicating that hydrogen bonding can shield hydrogens from exchanging with the bath gas D2S. The same HDX assay is applied here to investigate nucleic acid hairpin structure. Variations in hairpin solution‐phase stabilities are achieved by changing their loop size, stem length, and stem composition (ratio of G/C and A/T(U) base pairs in the stem). These differences can be carried into the gas phase because electrospray ionization is a gentle ionization method that is able to preserve noncovalent interactions. Observed gas‐phase HDX rates of these hairpins are consistent with their relative solution‐phase stabilities as predicted by MFold, i.e., less stable nucleic acid hairpins exchange faster than more stable hairpins. To our knowledge, the presented experiments demonstrate for the first time that gas‐phase HDX may be used to characterize nucleic acid higher order structure and the results suggest that the relative stabilities of nucleic acid hairpins in the gaseous phase are correlated with those in solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 256–264, 2009.
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19140156</pmid><doi>10.1002/bip.21134</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0006-3525 |
ispartof | Biopolymers, 2009-04, Vol.91 (4), p.256-264 |
issn | 0006-3525 1097-0282 |
language | eng |
recordid | cdi_proquest_miscellaneous_66882788 |
source | MEDLINE; Wiley Blackwell Journals |
subjects | Base Sequence Deuterium Exchange Measurement Gases - chemistry hydrogen exchange Mass Spectrometry Nucleic Acid Conformation nucleic acid structure Nucleic Acids - chemistry Solutions Solvents Spectroscopy, Fourier Transform Infrared |
title | Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T08%3A57%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20nucleic%20acid%20higher%20order%20structure%20by%20gas-phase%20H/D%20exchange%20in%20a%20quadrupole-FT-ICR%20mass%20spectrometer&rft.jtitle=Biopolymers&rft.au=Mo,%20Jingjie&rft.date=2009-04&rft.volume=91&rft.issue=4&rft.spage=256&rft.epage=264&rft.pages=256-264&rft.issn=0006-3525&rft.eissn=1097-0282&rft_id=info:doi/10.1002/bip.21134&rft_dat=%3Cproquest_cross%3E66882788%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=33099466&rft_id=info:pmid/19140156&rfr_iscdi=true |