Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.
Anfal MotibAntonio GuerreiroFiras Al-BayatiElena PiletskaIrfan ManzoorSulman ShafeeqAnagha KadamOscar KuipersLuisa HillerTodd CowenSergey PiletskyPeter W AndrewHasan YesilkayaPublished in: Angewandte Chemie (International ed. in English) (2017)
We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens.
Keyphrases
- molecularly imprinted
- gram negative
- drug discovery
- solid phase extraction
- mass spectrometry
- high performance liquid chromatography
- multidrug resistant
- antimicrobial resistance
- escherichia coli
- liquid chromatography
- candida albicans
- staphylococcus aureus
- deep learning
- high throughput
- gas chromatography
- tandem mass spectrometry