New methods for the bioorthogonal modification of proteins applied to the treatment of urinary tract infections

For over a century, the chemistry developed for the synthesis and production of new medical drugs and antibiotics by pharmaceutical companies was pioneered in a reaction flask in traditional organic solvents. However, in the 21st century the best selling drugs are no longer small molecules which can be made using traditional organic synthesis techniques, but biologics, which are macromolecules like proteins, enzymes, or antibodies that can act on their own or when they are fused to a small molecule drug.

The new challenges presented in the production of biologic medicines are that they cannot be treated in the same way as small molecules can, using harsh conditions like high temperature and aggressive solvents to drive reactions to completion- this is because these conditions are incompatible with the sensitive biological groups (e.g. amino acids and carbohydrates) present in biologics. Therefore synthetic methods have needed to be re-evaluated and redesigned so they take place selectively under mild, biological compatible conditions, such as in water, at neutral pH, and at body temperature. In such methods, speed and complete selectivity is of paramount importance because macromolecules contain much diverse chemical functionality which can interfere with the desired chemistry. Chemistry compatible with these constraints has been recently termed ‘bioorthogonal chemistry’- quite literally meaning chemistry orthogonal, or that which does not interfere, with other biological functionality and mechanisms.

In this proposal the student will adopt a novel multidisciplinary scientific approach consisting of a fusion between traditional small molecule organic chemistry, the evolving field of bioorthogonal chemistry, and the pharmaceutically relevant field of biologics development. This unique combination will facilitate the development of a new protein bioconjugation method which will be used to overcome the challenges of modifying proteins under biologically compatible conditions and utilised in the construction of a protein based anti-adhesion therapeutic for Uropathogenic E. coli (UPEC), the causative agent of urinary tract infections.

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview to take place at the University of York on Friday 12 May. Candidates will be asked to give a short presentation prior to their interview by an academic panel. All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills

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