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A new class of phosphinic protease inhibitor prodrug

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  • Full or part time
    Dr Matziari
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Requirements:
The candidate should have a first class or upper second class honours degree, or a master’s degree (or equivalent qualification), in Chemistry. Previous experience in Organic Synthesis is desirable. Evidence of good spoken and written English is essential. The candidate should have an IELTS score of 6.5 or above, or an equivalent qualification, if the first language is not English. This position is open to all qualified candidates irrespective of nationality.

Degree:
The student will be awarded a PhD degree from the University of Liverpool (UK) upon successful completion of the program.

Project Description:
Phosphinic peptides have been widely used for the study of proteases so as to elucidate their function in health and disease. They act as reversible, non-toxic, potent and selective inhibitors of proteases. Phosphinic peptides have been mostly used as metalloprotease inhibitors, although phosphinic inhibitors of aspartic acid proteases and other classes of enzymes such as ligases and kinases have also been reported. Some of the most interesting targets are Angiotensin Converting Enzyme (ACE) and Matrix Metalloproteases (MMPs). Nevertheless, the use of phosphinic acids as drugs presents a challenge with respect to their drug delivery. At physiological pH, phosphinic acids are negatively charged and due to their polarity are unable to penetrate cell membranes. To overcome this problem, esters have been used as prodrugs. These esters should meet several requirements, such as chemical stability and solubility of the prodrug in the gastrointestinal tract, good permeability across cell membranes, and finally efficient release of the drug at the target. Though several kinds of such phosphinate esters have been developed, and have been used in clinical trials, or are already in the market, sugar-based esters have never been used so far for phosphinic acids. It is anticipated that such an approach would be quite effective, since sugars have been used successfully before as pro-drug candidates, due to their hydrophilic properties. The aim of this project is to develop phosphinic peptide and non-peptide structures that show activity towards important enzyme targets, such as ACE (hypertension), MMPs (cancer), HIV proteases (AIDS), and Plasmepsins (malaria). The plan is to convert these phosphinic acids to esters using sugars and study the cell permeability and efficacy (antimalarial and antiviral properties) and whole animal disposition of both parent-drugs and their pro-drugs systems.

For more information about doctoral scholarship and PhD programme at Xi’an Jiaotong-Liverpool University (XJTLU): Please visit

http://www.xjtlu.edu.cn/en/admissions/postgraduate/phd-degree/ feesscholarships.html
http://www.xjtlu.edu.cn/en/admissions/postgraduate/phd-degree.html.

How to Apply:
Interested applicants are advised to email the following documents to [email protected] (please put the project title and primary supervisor’s name in the subject line).
- CV
- Two reference letters
- Personal statement outlining your interest in the position
- Proof of English language proficiency (an IELTS score of above 6.5 or equivalent is required
- Verified school transcripts in both Chinese and English (for international students, only the English version is required)
- Verified certificates of education qualifications in both Chinese and English (for international students, only the English version is required)

Informal enquiries may be addressed to Dr. Magdalini Matziari ([email protected]), whose personal profile is linked below;
http://academic.xjtlu.edu.cn/chem/Staff/magdalini-matziari

Funding Notes

The PhD studentship is available for three years subject to satisfactory progress by the student. The award covers tuition fees for three years (currently equivalent to RMB 80,000 per annum) and provides a monthly stipend of 3500 RMB as a contribution to living expenses. It also provides up to RMB 16,500 to allow participation at international conferences during the period of the award. It is a condition of the award that holders of XJTLU PhD scholarships carry out 300-500 hours of teaching assistance work per year. The scholarship holder is expected to carry out the major part of his or her research at XJTLU in Suzhou, China. However, he or she is eligible for a research study visit to the University of Liverpool of up to three months, if this is required by the project.

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