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Title: Distinguishing Isomeric Cyclobutane Thymidine Dimers by Ion Mobility and Tandem Mass Spectrometry
Irradiation of the major conformation of duplex DNA found in cells (B form) produces cyclobutane pyrimidine dimers (CPDs) from adjacent pyrimidines in a head-to-head orientation (syn) with the C5 substituents in a cis stereochemistry. These CPDs have crucial implications in skin cancer. Irradiation of G-quadruplexes and other non-B DNA conformations in vitro produces, however, CPDs between non-adjacent pyrimidines in nearby loops with syn and head-to-tail orientations (anti) with both cis and trans stereochemistry to yield a mixture of six possible isomers of the T=T dimer. This outcome is further complicated by formation of mixtures of non-adjacent CPDs of dC=dT, dT=dC, and dC=dC, and successful analysis depends on development of specific and sensitive methods. Towards meeting this need, we investigated whether ion mobility mass spectrometry (IMMS) and MS/MS can distinguish the cis,syn and trans-anti T=T CPDs. Ion mobility can afford base-line separation and give relative mobilities that are in accord with predicted cross sections. Complementing this ability to distinguish isomers is MS/MS collisional activation where fragmentation also distinguishes the two isomers and confirms conclusions drawn from ion mobility analysis. The observations offer early support that ion mobility and MS/MS can enable the distinction of DNA photoproduct isomers.  more » « less
Award ID(s):
2003688
PAR ID:
10550448
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
Journal of the American Society for Mass Spectrometry
Volume:
35
Issue:
8
ISSN:
1044-0305
Page Range / eLocation ID:
1768 to 1774
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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