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Peptide modification for enhanced stability and selective delivery.


Project Description

Overview: A fully funded studentship is available with Prof. Joanna McGouran at Trinity College Dublin (http://joannamcgouran.wixsite.com/mysite). The project is in the field of chemical biology focusing on the synthesis of and testing of new modified cyclic peptides and their conjugates.

Background: Biologics in therapeutics is a huge growth area in the pharmaceutical industry. Due to the favourable properties of cyclic peptides these are an area of specific interest with 9 cyclic peptide drugs having been approved in the last 10 years. Somatostatin is a tumour targeting peptide which cyclises via a disulphide bond. It is an approved peptide therapeutic, and several further peptide-drug conjugates are currently undergoing clinical trials.

Project: To develop new methods for stabilising cyclic peptides through replacement of disulphide bonds and generating peptide drug conjugates. Novel replacements of disulphide bonds in peptides will confer high stability to tertiary peptide structures and allow site selective incorporation of a therapeutic payload/reporter group. Initial efforts will utilise 14mer peptide somatostatin as a pharmaceutically relevant model system. Later in the PhD there is scope to translate the methodology into more challenging antibody systems.

Research environment: You will work in a supportive interdisciplinary group in the Department of Chemistry. Our laboratory is located within the Trinity Biomedical Sciences Institute, a dynamic, multidisciplinary research environment. You will join a vibrant research community with world class research facilities and be given the opportunity to interact with complementary research groups and attend national and international conferences to present your results.

Requirements: Good university degree (1st or 2:1) in the field of Chemistry, Biochemistry or a related subject. Preference will be given to candidates with a demonstrable interest in chemical biology and/or significant lab experience. You must be highly motivated and able to work both independently and as part of a supportive team. Good knowledge of organic chemistry and an interest in research at the interface with biochemistry/molecular biology is required. Knowledge of protein expression and purification advantageous but not necessary as full training will be given to you in all aspects of the project.

Application: For further information or to apply please email a PDF copy of a brief cover letter and CV, to .

Funding Notes

This is a fully funded 4 year position. Funding covers EU fees and with a stipend of 16,000 euros per year for living costs. This PhD is funded through the SSPC and as such you will also be part of th centre for the duration of your PhD.

References

Background reading:
1. Kuan, S. L.; Wang, T.; Weil, T., Site-Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome. Chemistry 2016, 22 (48), 17112-17129.
2. Wang, T.; Wu, Y.; Kuan, S. L.; Dumele, O.; Lamla, M.; Ng, D. Y.; Arzt, M.; Thomas, J.; Mueller, J. O.; Barner-Kowollik, C.; Weil, T., A disulfide intercalator toolbox for the site-directed modification of polypeptides. Chemistry 2015, 21 (1), 228-38.
3. Chudasama, V.; Maruani, A.; Caddick, S., Recent advances in the construction of antibody-drug conjugates. Nat Chem 2016, 8 (2), 114-9.
4. Krall, N.; da Cruz, F. P.; Boutureira, O.; Bernardes, G. J., Site-selective protein-modification chemistry for basic biology and drug development. Nat Chem 2016, 8 (2), 103-13.
5. Mangold, S. L.; O'Leary, D. J.; Grubbs, R. H., Z-Selective olefin metathesis on peptides: investigation of side-chain influence, preorganization, and guidelines in substrate selection. J Am Chem Soc 2014, 136 (35), 12469-78.

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