| Title | Tandem Mass Spectrometry Reveals Preferential Ruthenation of Thymines in Human Telomeric G-Quadruplex DNA by an Organometallic Ruthenium Anticancer Complex |
| Authors | Huang, Chao Ma, Ziqi Lin, Jiafan Gong, Xianxian Zhang, Fengfeng Wu, Xiaoqin Wang, Fuyi Zheng, Wei Zhao, Yao Wu, Kui |
| Affiliation | Wuhan Univ Sci & Technol, Key Lab Hubei Prov Coal Convers & New Carbon Mat, Sch Chem & Chem Engn, Wuhan 430081, Peoples R China Chinese Acad Sci, Beijing Natl Lab Mol Sci, Natl Ctr Mass Spectrometry Beijing, Beijing 100190, Peoples R China Chinese Acad Sci, CAS Key Lab Analyt Chem Living Biosyst, Inst Chem, Beijing 100190, Peoples R China Univ Chinese Acad Sci, Beijing 100049, Peoples R China Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China |
| Keywords | METAL-COMPLEXES QUARTET STRUCTURES SELECTIVE BINDING CRYSTAL-STRUCTURE ARENE COMPLEXES NUCLEIC-ACIDS IN-VITRO OLIGONUCLEOTIDES RECOGNITION INHIBITION |
| Issue Date | 28-Sep-2020 |
| Publisher | ORGANOMETALLICS |
| Abstract | The interaction of the organometallic ruthenium(II) anticancer complex [(eta(6)-biphenyl)Ru(en)Cl][PF6] (1; en = ethylenediamine) and a 22-mer human telomeric G-quadruplex (G4) DNA (sequence 5'-A(1)GGGTTAGGGTTAGGGTTAGGG(22)3'; I) was investigated by mass spectrometry analysis. Electrospray ionization mass spectrometry (ESI-MS) was first applied to probe the interaction of complex 1 with an equal molar ratio of human telomeric G-quadruplex DNA I (G4-I) under negative-ion mode. Tandem mass spectrometry using collision-induced dissociation (CID) was further introduced to identify the ruthenation sites. Primary mass spectrometric results showed that monoruthenated and diruthenated G4-I adducts were the main products under the given conditions. MS/MS results by the CID fragmentation of monoruthenated G4-I indicated that ruthenium complex 1 binds at T-17 or T-6 on G4-I. Further fragmentation of diruthenated G4-I confirmed preferential ruthenation at both T(17 )and T-6, while no ruthenation at the guanine base was observed. This is the first report to identify the binding sites of organometallic ruthenium(II) anticancer complexes to human telomeric G-quadruplex DNA using tandem MS. Given the preferential binding of complex 1 at guanine bases of ssDNA and dsDNA, the preferential ruthenation of thymine over guanine in the G-rich human telomeric DNA implicates that thymines located in the flexible loops are more likely to be involved in interactions of the organometallic ruthenium anticancer complex with telomeric DNA when the guanine bases are engaged in the G-quartets of the G-quadruplex DNA. |
| URI | http://hdl.handle.net/20.500.11897/592611 |
| ISSN | 0276-7333 |
| DOI | 10.1021/acs.organomet.0c00399 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
