- Phd Project Candidate A Bioisostere Approach For The Development Of Antibiotics With Optimized Adme Properties

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2013-09-25 02:00:30

PhD Project Candidate A bioisostere approach for the development of antibiotics with optimized ADME properties

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PhD Project Candidate A bioisostere approach for the development of antibiotics with optimized ADME properties

We have an open position for a PhD candidate at the Department of Medicinal Chemistry, Uppsala University, Sweden (http://www.orgfarm.uu.se). This project is part of the EU-funded project ARIADME: Analytical Research in ADME profiling (http://pharm.kuleuven.be/pharbio/ariadme). ARIADME is a Marie Curie project which involves 4 academic centers and 10 industrial partners. The PhD candidate will be enrolled in the UU doctoral school program and is expected to contribute to network wide training events of the ARIADME project. The scientific objectives and tasks of this 5-year PhD research project can be summarized as follows.

Objectives:

The broadest definition of bioisosteres is âgroups or molecules which have chemical and physical similarities producing broadly similar biological propertiesâ. Bioisosteric replacement is a useful strategy in drug discovery and development to improve ADMET properties. There is a large interest in the development of drugs that target phosphate containing substrates, especially new antibiotics and antiviral compounds. However, incorporation of a phosphate group into a molecule is normally unattractive since the negatively charged group renders the molecule impermeable to biological membranes. Consequently this is one of the most challenging functional groups to substitute and there is a significant interest in the identiication of phosphate alternatives. The overall aim of this research project is:

To design, synthesize and evaluate phosphate bioisosteres with improved ADME properties.

Main Tasks:

Density Functional Theory calculations and molecular modelling for evaluation andÂ design of new phosphate/phosphonate bioisosteres.
Organic synthesis and characterization of 1) model compounds carrying phosphate/phosphonate bioisosteres and 2) new TB antibiotics, including ADMET profiling by in silico and experimental methods.
Microwave-flow synthesis for production of synthetic building blocks and new TB antibiotics.

Formal requirements:

The highly motivated candidate should hold an MSc degree in Pharmaceutical Sciences, Chemical sciences or a related field. Applications should be sent to Prof. Mats Larhed (mats.larhed@orgfarm.uu.seÂ via the Apply button below) and include Resume/CV and Cover Letter.

The candidate should have less than 4 years' of research experience and must not have resided or carried out his/her main activity in Sweden for more than 12 months during the 3 years immediately prior to the recruitment.Â This is due to an EU funding stipulation.

Closing date: 31st October 2013

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