Document Detail


Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer.
MedLine Citation:
PMID:  19140156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 D(2)S. 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.
Authors:
Jingjie Mo; Gabrielle C Todd; Kristina Håkansson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biopolymers     Volume:  91     ISSN:  0006-3525     ISO Abbreviation:  Biopolymers     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-02-03     Completed Date:  2009-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372525     Medline TA:  Biopolymers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  256-64     Citation Subset:  IM    
Copyright Information:
2008 Wiley Periodicals, Inc.
Affiliation:
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109-1055, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Deuterium Exchange Measurement*
Gases / chemistry*
Mass Spectrometry
Nucleic Acid Conformation*
Nucleic Acids / chemistry*
Solutions
Solvents
Spectroscopy, Fourier Transform Infrared
Chemical
Reg. No./Substance:
0/Gases; 0/Nucleic Acids; 0/Solutions; 0/Solvents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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