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Synthesis of compounds to interact with i-Motif DNA

Information

  • Start date: October 2013
  • Programme: PhD
  • Mode of Study: Full Time
  • Studentship Length: 3 years

How to Apply

  • Deadline: 31 July 2013. Applications are processed as soon as they are received, so early application is encouraged. NB applicants who wish to start their studies in October 2013 should submit their application by 31 July 2013 at the very latest. Applications received after this date will be considered for the January 2014 entry point if the project is still available.
  • Apply online

Fees & Funding

Entry Requirements

  • Acceptable First Degree:

    Chemistry, Biochemistry, Pharmacy

  • Minimum Entry Standard: 2:1

Project Description

Certain sequences of DNA can potentially form different structures compared to the well-known "twisted ladder" arrangement (i, ii). One example is the i-Motif which is formed from sequences rich in cytosine (iii). These types of structures have been utilised in DNA-based nanotechnology but there is mounting evidence to suggest that the formation of alternative secondary structures can alter gene function, i.e. switching genes on or off (ii, iv). Targeting i-Motif forming DNA sequences with small molecules could lead to possible therapeutics for many different genetic disorders and diseases, including cancer but there are currently no specific small molecule ligands to interact with these structures. The project will involve chemical synthesis of new ligands to target i-Motif DNA structures. 

References

Nikolova, E. N.; Kim, E.; Wise, A. A.; O'Brien, P, J.; Andricioaei, I.; Al-Hashimi, H. M. Nature, 2011, 470, 498-502

T. A. Brooks, S. Kendrick, L. Hurley, FEBS J. 2010, 277, 3459

Gehring, K.; Leroy, J. L.; Gueron, M. Nature 1993, 363, 561

R. Rodriguez, K. M Miller, J. V Forment, C. R Bradshaw, M. Nikan, S. Britton, T. Oelschlaegel, B. Xhemalce, S. Balasubramanian, S. P Jackson, Nat. Chem. Biol. 2012, 5, 301



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