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Dr Yao Xu

Profile summary

  • Central Academic Staff
  • Senior Lecturer
  • Faculty of Science, Technology, Engineering & Mathematics
  • School of Life, Health & Chemical Sciences
  • yao.xu

Professional biography

Senior Lecturer in School of Life, Health and Chemical Sciences.

 

My research is in the area of chemistry of nucleic acids (DNA) and its applications to biological and medicinal sciences.

 

Research interests

Development of novel methods for the preparation of modified oligonucleotides (DNA and RNA); Application of the synthetic oligonucleotides in a wide variety of biological studies, particularly in DNA damage and repair.

Chemical synthesis and biochemical applications of base-modified DNA
We have been developing new methods for preparation of base-modified oligomers and using these modified oligomers for biological studies, in particular for DNA repair studies. A review was written to offer our insights into this type of work (see Xu, 2002) and recently a novel method was published for site-specific modification of purines in DNA (see Narukulla, Nucleic Acids Res., 2005 and Magnetic Resonance In Chemistry, 2008, Zhang, Magnetic Resonance In Chemistry, 2013 and 2016). 

Photoactivation of UVA-sensitive DNA as a novel cancer therapy
We have developed various methods for chemical synthesis of DNA containing thiobase (4-thiothymine and 6-thioguanine) at the predetermined positions. The thiobases are sensitive to UVA light (the UV light with the wavelength over 320 nm). Our recent exploration of these thiobase DNA resulted in exciting findings that thiopurines can be readily oxidized to produce harmful radicals which cause damages to DNA and proteins (see O'Donovan, Science, 2005; Zhang, DNA repair, 2007; Ren, NAR and Photochem and photobiology, 2010, Moore, PLoS one 2017) and that the cells containing thiothymine are highly susceptible to destruction upon UVA light (See Massey, Current Biology, 2001 and DNA repair, 2002 , Harada, JPC, 2007, Reelfs, MCT, 2007, Harada, JPCL, 2010, Pridgeon, 2011 and Gemenetzidis, 2013). These findings present a novel approach for targeting cancer cells with minimal damage to normal cells. We further exploit the approach for cancer studies (see Xu, BMCL, 2004, Zhang 2015, Chemical Letters, 2015, Ge, Progress in Chemistry 2016 and Zhang, RSC Advances 2016). Recent work with Prof. Suzuki on thioguanine analogues offers new insights to their photochemistry and potential applications (Miyata, Photomedicine and Photobiol., 2018; Photochem. Photobiol., 2018; J. Phys. Chem. B, 2018; Photochem & Photobiol. Sciences, 2018).

 

Teaching interests

Interests in teaching Organic Chemistry, Bio-organic and Medicinal chemistry.

I am the qualification lead for Medicinal Chemistry (masters level), the course team chair for Molecules in Medicine (S807) and for Concept to Clinic (S827). A recent review by Future Medicinal Chemistry on our medicinal chemistry education can be found from the link below: http://www.future-science.com/doi/full/10.4155/fmc.14.51

I am also the chair for undergraduate courses: Molecules, medicinas and drugs: a chemical stroy (SK185, level 1 short module) and Chemistry: essential concepts" (S215, levle 2 general chemistry).

Research groups

NameTypeParent Unit
Biomedical Research Network (BRN)NetworkFaculty of Science

Publications

SARS-CoV-2 Main Protease Inhibitors: Structure-Based Enhancement to Anti-Viral Pre-Clinical GC376 Encourages Further Development (2023)
Perry, Elliot D.; Chapman, Simon and Xu, Yao-Zhong
Journal of Computational Biophysics and Chemistry, Article 22 ((Early Access))

Adenine Quadruplexes Show Surprising Stability: Potential Implications for SARS-CoV-2 (2021-11)
Chapman, Simon; Ghesquiere, Pierre; Perry, Elliot; Taylor, Peter Geoffrey; Power, Nicholas P.; Sansom, Clare E. and Xu, Yao-Zhong
Journal of Computational Biophysics and Chemistry, 20(7) (pp. 675-685)

Excited States of Thio-2′-deoxyuridine Bearing an Extended π-Conjugated System: 3′,5′-Di-O-acetyl-5-phenylethynyl-4-thio-2′-deoxyuridine (2021)
Nonoshita, Daiki; Kashihara, Wataru; Tanabe, Kazuhito; Isozaki, Tasuku; Xu, Yao−Zhong and Suzuki, Tadashi
The Journal of Physical Chemistry A, 125(2) (pp. 597-606)

Simultaneous Two-Photon Absorption of the Thioguanosine Analogue 2′,3′,5′-Tri‑O‑acetyl-6,8-dithioguanosine with Its Potential Application to Photodynamic Therapy (2020-08-20)
Ando, Saki; Isozaki, Tasuku; Xu, Yao-Zhong and Suzuki, Tadashi
The Journal of Physical Chemistry A, 124(35) (pp. 7024-7030)

Characteristics of the Excited Triplet States of Thiolated Guanosine Derivatives and Singlet Oxygen Generation (2018-10-01)
Miyata, Shoma; Tanabe, Shunsuke; Isozaki, Tasuku; Xu, Yao-Zhong and Suzuki, Tadashi
Photochemical & Photobiological Sciences, 17(10) (pp. 1469-1476)

Absorption Characteristics and Quantum Yields of Singlet Oxygen Generation of Thioguanosine Derivatives (2018-07-03)
Miyata, Shoma; Yamada, Takeshi; Isozaki, Tasuku; Sugimura, Hideyuki; Xu, Yao-Zhong and Suzuki, Tadashi
Photochemistry and Photobiology, 94(4) (pp. 677-684)

Acid Dissociation Equilibrium and Singlet Molecular Oxygen Quantum Yield of Acetylated 6,8–Dithioguanosine in Aqueous Buffer Solution (2018)
Miyata, Shoma; Hoshino, Mina; Isozaku, Tasuku; Yamada, Takeshi; Sugimura, Hideyuki; Xu, Yao-Zhong and Suzuki, Tadashi
Journal of Physical Chemistry B, 122(11) (pp. 2912-2921)

Formation of oxidative photoproduct of tri-acetyl-modified 6-thioguanosine by UVA irradiation (2018)
Miyata, Shoma; Aoki, Ui; Tanabe, Shunsuke; Isozaki, Tasuku; Xu, Yao-Zhong. and Suzuki, Tadashi
Photomedicine and photobiology, 39 (pp. 15-18)

The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch (2017-09-14)
Moore, Elaine Ann and Xu, Yao-Zhong
PLoS ONE, 12, Article e0184801(9)

NMR studies on 4-thio-5-furan-modified and 4-thio-5-thiophene-modified nucleosides (2016-11)
Zhang, Xiao-Hui and Xu, Yao-Zhong
Magnetic Resonance in Chemistry, 54(11) (pp. 887-892)

The Synthesis of (E)-4-Thio-5-(2-Bromovinyl)Uridine/Deoxyuridine and Its Characterization and Cytotoxicity (2016-08-12)
Zhang, Xiaohui; Yan, Defeng; Ma, Kedong; He, Lingshuang; Gao, Ruiqi; Xu, Yaozhong and Li, Depeng
Chinese Journal of Organic Chemistry, 36(12) (pp. 2989-2996)

UVA Assisted 4-Thiothymidine for Cancer Treatment (2016-08)
Ge, Jiang; Feng, Luo; Yaozhong, Xu and Xiaohui, Zhang
Progress in Chemistry, 28(8) (pp. 1224-1237)

Synthesis of 4-thio-5-(2′′-thienyl)uridine and cytotoxicity activity against colon cancer cells in vitro (2016-07-19)
Zhang, Xiaohui; Li, Depeng; Qin, Jianzhong; Xu, Yaozhong and Ma, Kedong
RSC Advances, 6(74) (pp. 70099-70105)

UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions (2015-04-30)
Brem, Reto; Zhang, Xiaohui; Xu, Yao-Zhong and Karran, Peter
Journal of Photochemistry and Photobiology B: Biology, 145(4) (pp. 1-10)

5-iodo-4-thio-2′-deoxyuridine: synthesis, structure, and cytotoxic activity (2015-02)
Zhang, Xiao-Hui; Yin, Hong-Yan; Trigiante, Joseph; Brem, Reto; Karran, Peter; Pitak, Mateusz B.; Coles, Simon J. and Xu, Yao-Zhong
Chemistry Letters, 44(2) (pp. 147-149)

Spotlight on medicinal chemistry education (2014)
Pitman, Simone; Xu, Yao; Taylor, Peter and Turner, Nicholas
Future Medicinal Chemistry, 6(8) (pp. 865-869)

Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides (2013-08)
Zhang, Xiaohui; Wang, Jian and Xu, Yao-Zhong
Magnetic Resonance in Chemistry, 51(9) (pp. 523-529)

Topical 4-thiothymidine is a viable photosensitiser for the photodynamic therapy of skin malignancies (2013-06)
Gemenetzidis, Emilios; Shavorskaya, Oksana; Xu, Yao-Zhong and Trigiante, Giuseppe
Journal of Dermatological Treatment, 24(3) (pp. 209-214)

Study on synthesis and fluorescence spectra of 5-bromor-4-thio-2′-deoxyuridine labeled with monobromobimanes fluorescein (2011-12)
Yin, Hong-yan; Zhang, Xiao-hui and Xu, Yao-zhong
Journal of Molecular Science, 27(6) (pp. 397-401)

NMR and UV studies of 4-Thio-2′-deoxyuridine and its derivatives (2011-07-01)
Zhang, Xiaohui and Xu, Yao-Zhong
Molecules, 16(7) (pp. 5655-5664)

Thiothymidine combined with UVA as a potential novel therapy for bladder cancer (2011-06-07)
Pridgeon, S. W.; Heer, R.; Taylor, G. A.; Newell, D. R.; O'Toole, K.; Robinson, M.; Xu, Y-Z; Karran, P. and Boddy, A. V.
British Journal of Cancer, 104(12) (pp. 1869-1876)

Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells (2011)
Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter and Young, Antony R.
Nucleic Acids Research, 39(22) (pp. 9620-9632)

Photo-oxidation of 6-thioguanine by UVA: the formation of addition products with low molecular weight thiol compounds (2010-09)
Ren, Xiaolin; Xu, Yao-Zhong and Karren, Peter
Photochemistry and Photobiology, 86(5) (pp. 1038-1045)

UVA light-assisted anticancer drugs - study on 4-thiothymidine and its analogues (2010-05)
Zhang, X. H.; Wang, A. L.; Li, D. P. and Xu, Y.-Z.
Progress in Chemistry, 22(5) (pp. 784-795)

Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation (2010-04)
Ren, Xiaolin; Li, Feng; Jeffs, Graham; Zhang, Xiaohong; Xu, Yao-Zhong and Karran, Peter
Nucleic Acids Research, 38(6) (pp. 1832-1840)

Ultrafast intersystem crossing of 4-Thiothymidine inaqueous solution (2010)
Harada, Yosuke; Okabe, Chie; Kobayashi, Takashi; Suzuki, Tadashi; Ichimura, Teijiro; Nishi, Nobuyuki and Xu, Yao-Zhong
Journal of Physical Chemistry Letters, 1(2) (pp. 480-484)

Unambiguous structural elucidation of base-modified purine nucleosides using NMR (2008-01)
Narukulla, Raman; Shuker, David E. G.; Ramesh, Vasudevan and Xu, Yao-Zhong
Magnetic Resonance in Chemistry, 46(1) (pp. 1-8)

Reactive oxygen-mediated damage to a human DNA replication and repair protein (2007-10-12)
Montaneri, Beatriz; O'Donovan, Peter; Reelfs, Olivier; Perrett, Conal M; Zhang, Xiaohong; Xu, Yao-Zhong; Ren, Xiaolin; Macpherson, Peter; Frith, David and Karran, Peter
EMBO Reports, 8(11) (pp. 1074-1079)

Thiothymidine plus low-dose UVA kills hyperproliferativehuman skin cells independently of their human papilloma virus status (2007-09-01)
Reelfs, Olivier; Xu, Yao-Zhong; Massey, Andrew; Karran, Peter and Storey, Alan
Molecular Cancer Therapeutics, 6 (pp. 2487-2495)

Triplet Formation of 4-Thiothymidine and Its Photosensitization to Oxygen Studied by Time-Resolved Thermal Lensing Technique (2007-04)
Harada, Y; Suzuki, T; Ichimura, T and Xu, YZ
Journal of Physical Chemistry B, 111(19) (pp. 5518-5524)

Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light (2007-03-01)
Zhang, Xiaohong; Jeffs, Graham; Ren, Xiaolin; O'Donovan, Peter; Montaner, Beatriz; Perrett, Conal M.; Karran, Peter and Xu, Yao-Zhong
DNA Repair, 6(3) (pp. 344-354)

Azathioprine and UVA Light generate mutagenic oxidative DNA damage (2005-09-16)
O'Donovan, Peter; Perrett, Conal M.; Zhang, Xiaohong; Montaner, Beatriz; Xu, Yao-Zhong; Harwood, Catherine A.; McGregor, Jane M.; Walker, Susan L.; Hanaoka, Fumio and Karran, Peter
Science, 309(5742) (pp. 1871-1874)

Post-synthetic and site-specific modification of endocyclic nitrogen atoms of purines in DNA and its potential for biological and structural studies (2005-03)
Narukulla, Raman; Shuker, David E.G. and Xu, Yao-Zhong
Nucleic Acids Research, 33(6) (pp. 1767-1778)

Evidence for three thymine DNA glycosylases in human cell extracts: substrate specific cities of thymine DNA glycosylase activities (2005-02)
Lari, Sibghat-Ullah; Xu, Yao-Zhong and Day, Rufus S.
Medical Science Monitor, 11(2) (pp. 41-49)

4-Thio-5-bromo-2′-deoxyuridine: chemical synthesis and therapeutic potential of UVA-induced DNA damage (2004-02-23)
Xu, Yao-Zhong; Zhang, Xiaohui; Wu, Hai-Chen; Massey, Andrew and Karran, Peter
Bioorganic and Medicinal Chemistry Letters, 14(4) (pp. 995-997)

Ambiguous coding is required for the lethal interaction between methylated DNA bases and DNA mismatch repair (2002-04-29)
Massey, Andrew; Xu, Yao-Zhong and Karran, Peter
DNA Repair, 1(4) (pp. 275-286)

Photoactivation of DNA thiobases as a potential novel therapeutic option (2001-07-24)
Massey, Andrew; Xu, Yao-Zhong and Karran, Peter
Current Biology, 11(14) (pp. 1142-1146)

Nucleotides and oligonucleotides: mononucleotides (2015-04)
Narukulla, Raman and Xu, Yao-Zhong
In: Allen, David; Tebby, John C. and Loakes, David eds. Organophosphorus Chemistry (pp. 170-192)
ISBN : 978-1-78262-111-9 | Publisher : The Royal Society of Chemistry | Published : Cambridge

4-thiothymidine and its analogues as UVA-activated photosensitizers (2015-03)
Trigiante, Guiseppe and Xu, Yao-Zhong
In: Hugo, Adrian G. ed. Photodynamic Therapy: Fundamentals, Applications and Health Outcomes. Cancer Etiology, Diagnosis and Treatments (pp. 193-206)
ISBN : 978-1-63463-857-9 | Publisher : Nova SciencePublishers | Published : Hauppauge, NY

Nucleotides and oligonucleotides: mononucleotides (2014-04)
Xu, Yao-Zhong and Narukulla, Raman
In: Allen, David; Tebby, John C. and Loakes, David eds. Organophosphorus Chemistry (pp. 117-145)
ISBN : 978-1-84973-942-9 | Publisher : The Royal Society of Chemistry | Published : Cambridge

Synthetic chemistry of base-modified DNA and their biological applications (2002)
Xu, Yao-Zhong
In: Loakes, David ed. Modified Nulceoside, Synthesis and Applications (pp. 1-16)
ISBN : 81-7736-121-X | Publisher : Research Signpost | Published : Kerala, India