There are examples of small molecules that have intra cellular targets in Gram positive bacteria but very little information about targeting the outer Peptidoglycan layer. Are there any well established targeting ligands that could potentially be used to transport a Nanoparticle to Peptidoglycan cell wall?
There are antibiotics that bind the peptidoglycan, such as vancomycin and teicoplanin.
The penicillin-binding proteins (PBPs) are in the inner membrane beneath the thick Gram-positive peptidoglycan layer. If you think you can get your nanoparticles through the peptidoglycan, then beta-lactams could be used to target them to the PBPs, forming a covalent bond. It would be easy to attach ampicillin to a linker to the nanoparticles, since it has a primary amino group.
Adam B Shapiro Thank you for your input. Vancomycin and teicoplanin are some of the molecules that I have been looking into. However, we are working towards developing nanoparticle based solutions for bacterial infections as an alternative to antibiotics. So using an antibiotic to target the cell would defeat the purpose. I can, however look into mechanistic details of how the antibiotic targets the PG layer and mimic those functional group features of the drug. I also have to look into the details of how the bacterial cells develop resistance against such molecules and try to find solutions for that in the targeting molecule.
I would love to hear your thoughts on this.
Adam B Shapiro Penicillin binding proteins are an interesting idea but I believe my nanoparticles are too large to go through the PG layer. I can very easily put the targeting group on a PEG chain of about 5KDa. I will find out whether the chains would be long enough to go through the PG layer without the rod having to penetrate the layer. Thanks a lot for you thoughts I have a lot to think about now and I believe I am at a better place than before thanks to your help.
Resistance to vancomycin arises from a modification of the structure of the peptidoglycan, reducing the binding affinity of vancomycin, and teicoplanin in some cases.
https://en.wikipedia.org/wiki/Vancomycin-resistant_Enterococcus
Article Vancomycin Resistance VanS/VanR Two-Component Systems
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Peptides