TD: Cationic Antimicrobial Peptides PPT Flashcards
What are the structure of antimicrobial peptides?
The structure adopted by the peptides appears to be crucial for their activity.
Generally rich in proline and arginine, positively charged and display amphiphilic (hydrophilic and hydrophobic) character.
What is the mode of action of AMPs?
One of the proposed modes of direct antimicrobial action of cationic AMPs involves electrostatic interaction between the positively charged peptides and the negatively charged bacterial cytoplasmic membrane (mammalian cell membranes are uncharged).
This interaction damages the bacterial membrane, forming non-specific pores, leading to leakage and death.
Some have also been found to enter the cell and binding to DNA, disturbing bacterial physiological activity.
Some cationic AMPs have also been shown to interact with fungal organelles such as mitochondria leading to their death.
As well as these direct effects, some cationic AMPs demonstrate indirect antimicrobial effects by participate in immune modulation.
What is an example of a naturally occuring AMP?
What is its funtions?
Defensins are “moonlighting peptides”, so called because each peptide has more than one important role in human health and disease.
These include immuno-regulatory functions as well as at mM concentrations they display broad spectrum antimicrobial action against Gram +ve/-ve bacteria, fungi and some enveloped viruses.
What would need to be changed and why if developing therapeutic AMPs from those naturally occuring?
However these naturally-occurring AMPs tend to lack stability and to have a short shelf-life so therapeutic versions would probably require modification to produce longer-acting peptide analogues.
Postive of AMPs
- Structurally diverse,
- Show rapid bactericidal action,
- Thermally stable,
- Water soluble,
- Have a broad spectrum of activity that includes most of the clinically important resistant bacteria,
- May be antifungal/antiviral/anti-endotoxin/anti-cancer
- Can promote wound healing.
- Low reported frequency of resistance development
Negatives of AMPs
- Long-term use of some AMPs may lead to negative side effects.
- Finding suitable therapeutic AMPs is time-consuming, expensive and depends the building of databases of their structure and antimicrobial properties, and making these available to researchers.
What is an example of an AMP in trials?
Brilacidin, has completed human phase 2 clinical trials. It is one of a new class of antibiotics called “host defence protein mimetics” - synthetic small-molecules modelled on human defensins. Trials of analogues of Brilacidin are in the pipeline
Being investigated as a potential COVID-19 candidate in combination with remdesivir
