This project aims to develop selective P. vivax NMT inhibitors as tools for probing biological features of the P. vivax parasite, and potential lead compounds for development of drug that targets multiple life cycle stages of the parasite.
We will use structure-based approaches to design hybrids of the previously reported inhibitors, taking physicochemical properties and potential differences of binding mode between human NMT1 and NMT2, and P. vivax NMT into account.
The activity of the compounds will be assessed against NMT1 and NMT2, and P. vivax NMT. Compounds with 30-fold selectivity will serve as a starting point for subsequent medicinal chemistry eﬀorts, by structure-activity-relationship (SAR) to optimise selectivity and affinity.
The best compounds will be further characterised in various assays.
The project aims to develop P. vivax NMT inhibitors with all the characteristics of high quality chemical probes. In future studies, these chemical probes may be applied to examine the role and druggability of P. vivax NMT and N-myristoylation in all stages of the parasite, including in the sexual blood stages and liver stages, which are important targets for blocking transmission. Furthermore, these inhibitors can be regarded as a candidate series for the treatment of malaria.
Learning outcome for the scholarship holder:
1) Heterocyclic chemistry as well as modern metalorganic chemistry.
2) Design of molecules using computational approaches.
3) Structure-Activity Relationship (SAR) studies.
4) Teamwork and project management.
5) Writing papers and give scientific presentations.
Dnr / Reference
The scholarship covers a period of 6 months with possibility of prolongation up to a maximum of 24 months in total.
Preliminary start date: 2020-12-01
Morten Grøtli, +46 766229017, firstname.lastname@example.org
- To be eligible for a post-doc scholarship at the Department of Chemistry and Department the recipient must hold a PhD degree within a relevant field. The applicant must not have been employed at University of Gothenburg in the past two years.
- The successful postdoctoral applicant should have significant and documented experience in medicinal chemistry, and preferably experience from antimalarial drug discovery, as well as using MOE for inhibitor design. In addition, the candidate must be self-motivated and able to work independently but also to work efficiently in a team setting.
Written application, including reference number, is to be sent via e-mail to the supervisor and must include the following:
- Personal letter stating the reasons why the study suits the applicant (maximum one page)
- List of publications
- References (2)
Application deadline: 2020-11-25
Information regarding scholarships
- Scholarships do not give rise to sickness benefits, compensation from the Social Insurance Office Agency or retirement pension.
- The scholarship sum is paid out at two occasions
- Scholarships are tax-exempt
- A scholarship holder cannot be employed after the scholarship period due to tax reasons.