Modification and Design of Antimicrobial Peptides against Superbugs
Antimicrobial peptides (AMPs) are a unique group of naturally occurring antimicrobial compounds. They are found in almost all organisms, have broad-spectrum antimicrobial activity, and have very low levels of resistance induction in bacteria, making them ideal targets for drug development and targeting of superbugs. However, the development of these peptides is also limited by instability, toxicity and bioavailability. Therefore, modification and design are hot spots in the research of AMPs in order to improve their performance.
Ace Therapeutics provides research services focused on modifying the structure, hydrophobicity, amphipathicity and charge of natural AMP sequences by modifying and designing them to improve antimicrobial activity and specificity while reducing cytotoxicity to address application limitations.
Potential of Modified AMPs to Fight Superbugs
AMPs exhibit strong antibacterial activity in vitro and in vivo. At least thousands of active natural AMPs have been identified, and despite their large number, their applications are limited in various ways. Manipulating the intrinsic properties of AMPs can help overcome the limitations. There are two main modification strategies, biochemical and chemical modifications. Chemical modifications are generic and straightforward and include forms such as lipidation, glycosylation and multimerization. Biochemical modifications allow heterologous expression of antimicrobial peptides.
Fig. 1 Various forms of multimerization of AMP. (Matthyssen T, et al., 2022)
Modified AMPs yield compounds with improved activity and biocompatibility compared to their linear counterparts, which makes them more desirable targets for targeting multi-drug resistant bacteria.
Services for Modification and Design of AMPs
We offer services for the modification and design of AMPs for superbugs, which can be found below. The purpose of our service is to help scientists address the application limitations of these unique AMPs and potentially create new molecules to overcome the shortcomings of natural AMPs.
Chemical modification of AMPs against superbugs
We combine the simplicity of peptide chemical synthesis with emerging molecular engineering principles to design AMPs with potent broad-spectrum activity against multi-drug resistant strains. we support molecular engineering approaches and design tools for peptide self-assembly to provide new directions for drug formulations. You can use these advances in our basic research to lay a solid foundation for rationally designed peptide antimicrobial agents that can be used as new drugs against multi-drug resistant strains.
Molecular engineering of AMPs against superbugs
We can support the isolation and characterization of bacteriocins from different bacterial species to explore in vitro activity against common superbugs such as Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridium difficile. Further, new molecules can be designed based on genetic peptide engineering to expand their use as antimicrobial agents.
Our Modifying Methods
- Change in amino acid type and sequence position
- Side chain length, d-amino acid and N-terminal modifications
- Peptide length change
- AMP-based polymer building, including dimers, dendrimers, stars, polymorphic compounds, etc.
- Ribosome engineering
- Genetic engineering
- Bioinformatic tools
In conclusion, the application of novel AMPs has shown great promise. Many of the AMPs previously found in nature are likely not directly available as commercial drugs against drug-resistant bacteria, or you have newly acquired compounds. Faced with these situations, you may need our modification and design services to generate innovative and effective tools that can be used to control drug-resistant bacteria.
Please do not hesitate to contact us for more services.
References
- Matthyssen T, et al. The Potential of Modified and Multimeric Antimicrobial Peptide Materials as Superbug Killers. Front. Chem., 2022, 9: 795433.
- Cardoso P, et al. Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities. Biophys Rev, 2021, 13, 35–69.