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Collision-Induced Dissociation Studies of Protonated Ions of Alkylated Thymidine and 2'-Deoxyguanosine.

ABSTRACT: Mass spectrometry and tandem MS (MS/MS) have been widely employed for the identification and quantification of damaged nucleosides in DNA, including those induced by alkylating agents. Upon collisional activation, protonated ions of alkylated nucleosides frequently undergo facile neutral loss of a 2-deoxyribose in MS/MS, and further cleavage of the resulting protonated nucleobases in MS³ can sometimes be employed for differentiating regioisomeric alkylated DNA lesions. Herein, we investigated systematically the collision-induced dissociation (CID) of the protonated ions of O⁴-alkylthymidine (O⁴-alkyldT), O²-alkyldT, O⁶-alkyl-2'-deoxyguanosine (O⁶-alkyldG), and N²-alkyldG through MS³ analysis. The MS³ of O²- and O⁴-MedT exhibit different fragmentation patterns from each other and from other O²- and O⁴-alkyldT adducts carrying larger alkyl groups. Meanwhile, elimination of alkene via a six-membered ring transition state is the dominant fragmentation pathway for O²-alkyldT, O⁴-alkyldT, and O⁶-alkyldG adducts carrying larger alkyl groups, whereas O⁶-MedG mainly undergoes elimination of ammonia. The breakdown of N²-alkyldG is substantially influenced by the structure of the alkyl group, where the relative ease in eliminating ammonia and alkene is modulated by the chain length and branching of the alkyl groups. We also rationalize our observations with density functional theory (DFT) calculations.

SUBMITTER: Cui Y

PROVIDER: S-EPMC7362892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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