Reversible and Fully Controllable Generation of Organo-Soluble DNA (osDNA).

The present work describes a complete and reversible transformation of DNA's properties allowing solubilization in organic solvents and subsequent chemical modifications that are otherwise not possible in an aqueous medium. Organo-soluble DNA (osDNA) moieties are generated by covalently linking a dsDNA fragment to a polyether moiety with a built-in mechanism, rendering the process perfectly reversible and fully controllable. The precise removal of the polyether moiety frees up the initial DNA fragment, unaltered, both in sequence and nature. The solubility of osDNA was confirmed in six organic solvents of decreasing polarity and six types of osDNAs. As a proof of concept, in the context of DNA-encoded library (DEL) technology, an amidation reaction was successfully performed on osDNA in 100% DMSO. The development of osDNA opens up entirely new avenues for any DNA applications that could benefit from working in nonaqueous solutions, including chemical transformations.

Effect of roadside trees on pedestrians' psychological evaluation of traffic noise.

Introduction: This study aims to investigate the interplay between roadside trees and pedestrians' assessment of traffic noise and comfort. The study examines the potential effects of visual and design elements of roadside trees on the overall soundscape comfort. Methods: The study design involves a systematic exploration of different conditions, encompassing traffic volume, distance from sound source, and tree density. For each combination, two experimental scenarios are created: (1) participants experience a binaural sound recording exclusively, and (2) participants experience the same binaural recording while concurrently immersed in a virtual reality (VR) video. Results: Analysis of participants' noise perception, measured using a quiet-noisy scale, reveals no significant disparity between conditions. This suggests that the mere presence of roadside trees does not necessarily lead to a perceived reduction in noise loudness. However, evaluation of sound intensity exposes a notable discrepancy between low and medium tree density levels. Furthermore, the study confirms the impact of roadside tree visibility, with scenes containing trees yielding more positive evaluations compared to sound-only scenarios. Remarkably, the absence of trees in the roadside scene garners consistent evaluations across both experimental conditions. Significantly, higher roadside tree density in conjunction with the combined sound and VR video condition prompts a more favorable assessment than the sound-only scenario. Discussion: While the study indicates that roadside trees might not substantially mitigate perceived physical noise levels, their influence on the psychological well-being of urban inhabitants is considerable. The findings highlight that even though these trees may not overtly diminish noise, they hold substantial potential to enhance the overall comfort and well-being of city residents. This underscores the multifaceted benefits of integrating green spaces into urban design for improving the quality of urban soundscapes and residents' experiences.

Impact of organic chemistry conditions on DNA durability in the context of DNA-encoded library technology.

High-power screening (HPS) technologies, such as DNA-encoded library (DEL) technology, could exponentially increase the dimensions of the chemical space accessible for drug discovery. The intrinsic fragile nature of DNA is associated with cumbersome limitations and DNA durability (e.g., depurination, loss of phosphate groups, adduct formation) is compromised in numerous organic chemistry conditions that require empirical testing. An atlas of reaction conditions (temperature, pH, solvent/buffer, ligands, oxidizing reagents, catalysts, scavengers in function of time) that have been systematically tested in multiple combinations, indicates precisely limits useful for DEL construction. More importantly, this approach could be used broadly to effectively evaluate DNA-compatibility of any novel on-DNA chemical reaction, and it is compatible with different molecular methodologies. This atlas and the general approach presented, by allowing novel reaction conditions to be performed in presence of DNA, should greatly help in expanding the DEL chemical space as well as any field involving DNA durability.

DNA-Compatible Suzuki-Miyaura Cross-Coupling Reaction of Aryl Iodides With (Hetero)Aryl Boronic Acids for DNA-Encoded Libraries.

An efficient method for the C-C bond formation via water soluble Na2PdCl4/sSPhos mediated Suzuki-Miyaura cross-coupling reaction of DNA-conjugated aryl iodide with (het)aryl boronic acids has been developed. This reaction proceeds at 37°C in water and acetonitrile (4:1) system. We also demonstrated that numerous aromatic and heteroaromatic boronic acids of different electronic natures, and harboring various functional groups, were highly compatible providing the desired coupling products in good to excellent yields. This DNA-compatible Suzuki-Miyaura cross-coupling reaction has strong potential to construct DNA-Encoded Libraries (DELs) in the context of drug discovery.

High-power screening (HPS) empowered by DNA-encoded libraries.

The world is totally dependent on medications. As science progresses, new, better, and cheaper drugs are needed more than ever. The pharmaceutical industry has been predominantly dependent on high-throughput screening (HTS) for the past three decades. Considering that the discovery rate has been relatively constant, can one hope for a much-needed sudden trend uptick? DNA-encoded libraries (DELs) and similar technologies, that have several orders of magnitude more screening power than HTS, and that we propose to group together under the umbrella term of high-power screening (HPS), are very well positioned to do exactly that. HPS also offers novel screening options such as parallel screening, ex vivo and in vivo screening, as well as a new path to druggable alternatives such as proteolysis targeting chimeras (PROTACs). Altogether, HPS unlocks novel powerful drug discovery avenues.

The Bacterial Hsp90 Chaperone: Cellular Functions and Mechanism of Action.

Heat shock protein 90 (Hsp90) is a molecular chaperone that folds and remodels proteins, thereby regulating the activity of numerous substrate proteins. Hsp90 is widely conserved across species and is essential in all eukaryotes and in some bacteria under stress conditions. To facilitate protein remodeling, bacterial Hsp90 collaborates with the Hsp70 molecular chaperone and its cochaperones. In contrast, the mechanism of protein remodeling performed by eukaryotic Hsp90 is more complex, involving more than 20 Hsp90 cochaperones in addition to Hsp70 and its cochaperones. In this review, we focus on recent progress toward understanding the basic mechanisms of bacterial Hsp90-mediated protein remodeling and the collaboration between Hsp90 and Hsp70. We describe the universally conserved structure and conformational dynamics of these chaperones and their interactions with one another and with client proteins. The physiological roles of Hsp90 in Escherichia coli and other bacteria are also discussed. We anticipate that the information gained from exploring the mechanism of the bacterial chaperone system will provide a framework for understanding the more complex eukaryotic Hsp90 system.