Design, synthesis and validation of a new Crimped Head-Piece for DNA-Encoded libraries generation.

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity.

The treatment of bacterial biofilms cultivated on knee arthroplasty implants using the bioelectric effect.

Introduction: The formation of bacterial biofilms on knee arthroplasty implants can have catastrophic consequences. The aim of this study was to analyze the effectiveness of the bioelectric effect in the elimination of bacterial biofilms on cultivated knee arthroplasty implants. Methods: A novel device was designed to deliver a bioelectric effect on the surface of knee arthroplasty implants. 4-femoral prosthetic implants were cultivated with a staphylococcus aureus inoculum for 15 days. The components were divided into four different groups: A (not treated), B (normal saline 20-minutes), C (bioelectric effect 10-minutes), D (bioelectric effect 20-minutes). The implants were sonicated, and the detached colonies were quantified as the number of colony-forming unit (CFUs). The implants were sterilised and the process was repeated in a standardized manner four more times, to obtain a total of five samples per group. Results: The number of the CFUs after a 10-minute exposure to the bioelectric effect was of 208.2 ± 240.4, compared with 6,041.6 ± 2010.7 CFUs in group A, representing a decrease of 96.5% ± 4.3 (p = 0.004). And a diminution of 91.8% ± 7.9 compared with 2,051.0 ± 1,364.0 CFUs in group B (p = 0.109). The number of bacterial colonies after a 20-minute exposure to the bioelectric effect was 70 ± 126.7 CFUs, representing a decrease of 98.9% ± 1.9 (p = 0.000) compared with group A. And a decrease of 97.8% ± 3.0 (p = 0.019) compared with group B. Conclusions: The bioelectric effect was effective in the elimination of bacterial biofilm from knee arthroplasty implants. This method could be used in the future as part of conventional surgical procedures.