Design, synthesis and characterization of antibiotic peptides
Research Area: Pharmaceutical Chemistry and Analysis
THIS IS A GENERAL IDEA OF THE LR
The challenge of multidrug resistance (MDR) has become a critical issue in treating bacterial infections. The continuous dissemination of MDR bacteria drastically reduces the efficiency of the antibiotic arsenal and consequently increases the frequency of therapeutic failure. One major component of resistance to many classes of antimicrobials as well as chemotherapeutic agents is multidrug efflux. Efflux transporters are found in both gram positive and gram negative bacteria, and actively remove chemical agents out of the cell. These transporters are protein complexes that are located in the cell envelope of the bacteria and with the function to pump any toxic substances from inside the cell to the exterior.
Antibacterial peptides are being studied as a solution to this problem however their potential toxicity and stability has limited advancements in their therapeutic use. The proposed work will therefore attempt to design a novel antimicrobial peptide (AMP) with dual functionality.
The main aim of this project is to rationally design modified antibacterial peptides that will have ability to act as efflux pump inhibitors and act synergistically with antibacterial agents against multidrug resistant bacteria. The designed molecules will be synthesized, characterized and tested against a range of multidrug strains. Candidates with promising activity will be used as for future development and design of peptidomimetic analogues.
1)Abstract (200 word limit)
Provide a summary of the work to be performed. You should include
• Introduction and justification of proposed work
• Aims and objectives
• Brief methodology
• Expected outcomes/anticipated benefits
2) Here is the expected outline for the LR with my supervisor comments (4000 words)
The general layout of the literature review should consist of the following
• Introduction
• review
• conclusions
Include tables/ figures and subsections if required.
Will there be a particular AMP or just right in general?
We will focus on AMPs that are active against Gram-negative bacteria.
As you can see there are two type cationic and proline rich peptides.
Their structures are going to be predicted using homology modelling to obtain their 3D arrangement of atoms. Those will be overlaid, to observe common features. The common features will provide basis to propose new sequences.
These sequences will be used to synthesize the novel peptides, and to characterize.
What do you recommend for This basic structure?

Infection and response Immune system
Gram negative
Types of antibiotics
AMPS types and potency
Problem rising from MDR bacteria
Why there is a need
Approaches to overcome these problems
Infection and response of the immune systems
Bacteria gram-negative
Treatments; Antibiotic types –why there is a need for new antibiotics
AMP - Types and Potency
Structure prediction of peptides. (use the methods in the following paper as a basis for the prediction of AMP structures)
Synthesis
Testing effectiveness
3)Proposal critique
To include a summary of the work and outline of the aims, and indication of how the proposal relates to current literature and its justification and appropriateness. Comment on ethical issues and statistical analysis if appropriate. (No more than1000 words)
Suggestions for a particular method?
No suggestions for a particular method, you will identify methods that you are using in the proposal, and then suggest if these methods are adequate, or if you may have a better solution.
4)References

Design, synthesis and characterization of antibiotic peptides Rese...