In a recent article published in the prestigious Journal of American Chemical Society, the groups of Prof. Gilles Gasser at the Institute of Chemistry for Life and Health Sciences at Chimie ParisTech-PSL in collaboration with Dr. Marcel Hollentstein from Institut Pasteur could demonstrate, for the first time, that the modification of aptamers (i.e., short DNA strands capable of binding to targets) with Ruthenium polypyridyl complexes allows selectively targeting Gram-positive Streptococcus pneumoniae bacteria, a very problematic strain in medicine. Thanks to the presence of these ruthenium complexes that can act as photosensitizers for photodynamic therapy, light can be used to activate them and eradicate the bacteria.
More precisely, this consortium of scientists could first prepare nucleotides equipped with various ruthenium complexes. They then demonstrated that some DNA polymerases could allow synthesising enzymatically oligonucleotides containing these Ruthenium complexes. Through a so-called SELEX experiment, one aptamer was found to have a high affinity (Kd value of 125 nM) for fixed Streptococcus pneumoniae bacteria. Collectively, these results, obtained after 7 years of work of 2 PhD students and one post-doc, highlight the possibility of using nucleotides equipped with large modifications such as ruthenium polypyridyl complexes in SELEX to raise potent aptamers against entire bacterial targets. These findings open directions to convert aptamers into potent devices to combat antimicrobial resistance via PDT-based approaches.
The article can be found on this link: https://doi.org/10.1021/jacs.5c13224
