AbstractWith the increasing emergency of drug-resistance, the AMPs from the amphibians have raised much interest due to their broad-spectrum antimicrobial activity and promising immunological competence. Among the many species of amphibians, Odorrana grahami was found to be one of the most abundant sources of skin AMPs.
In this thesis, three experimental chapters describe two peptide templates, the design of respective analogues and structure-activity studies conducted on different aspects and at different depths.
In Chapter 3, a novel peptide was obtained from the skin secretion of a frog. This peptide has broad-spectrum antimicrobial activity and potent anti-biofilm activity. As an important motif, the “Rana box” was hitherto considered as important in affecting the antimicrobial activity of parent peptide, while the role of the cationic residues in the “Rana box” has not been discussed before. This study revealed the significant role of the specific residues in the “Rana box” and reduced the significance of the “Rana box” in the antimicrobial activity of parent peptide family, which was accepted widely in previous studies.
In Chapter 4, the study here examines the imperfect/perfect amphipathic mode of a peptide. The parent peptide has a broad-spectrum antimicrobial activity against all the pathogens tested herein. Analogues of it exhibited advantages and disadvantages in many ways, mainly in their antimicrobial activity effects. This study has revealed the rationality of the imperfect amphipathic model and possibility of further modification targeting the residues of the hydrophobic face. Additionally, the disulfide bond also has been shown to have a special influence on anti-biofilm activity. Further structure-function relationship studies could be performed based on the bio-functionality data of these analogues presented here.
In Chapter 5, another peptide isolated from the same frog above, which was studied before and showed no antimicrobial activity, was revisited. This peptide, possessing lectin-like activity and specific immune system bio-functions, underwent structural modifications in an attempt to investigate structure-function relationships for analogue design as potential drug leads. However, these attempts proved unsuccessful.
Key word: Drug-resistance, Antimicrobial peptides, Amphibians, Brevinin-1 peptide family, Anti-biofilm peptides
Thesis is embargoed until 31 July 2028.
|Date of Award||Jul 2023|
|Supervisor||Lei Wang (Supervisor), Tianbao Chen (Supervisor) & Tao Wang (Supervisor)|
- antimicrobial peptides
- brevinin-1 peptide family
- anti-biofilm peptides