The covalent binding partners of the electrophilic natural products falcarinol and neocarzilins A-C were identified applying ABPP (Activity based protein profiling) in human cancer cells. Potential targets obtained by quantitative mass spectrometry were confirmed using activity based assays, imaging and binding site identification. The application of photocrosslinkers to identify noncovalent interactions and the synthesis of minimal photoprobes with embedded photoreactive moieties led to the identification of a whole proteome inventory of background photocrosslinker binding in human cancer cells.

Target identification of natural products by activity based protein profiling and a whole proteome inventory of background photocrosslinker binding

Chemically modified biomacromolecules-i.e., proteins, nucleic acids, glycans, and lipids-have become crucial tools in chemical biology. They are extensively used not only to elucidate cellular processes but also in industrial applications, particularly in the context of biopharmaceuticals. In order to enable maximum scope for optimization, it is pivotal to have a diverse array of biomacromolecule modification methods at one's disposal. Chemistry has driven many significant advances in this area, and especially recently, numerous novel visible-light-induced photochemical approaches have emerged. In these reactions, light serves as an external source of energy, enabling access to highly reactive intermediates under exceedingly mild conditions and with exquisite spatiotemporal control. While UV-induced transformations on biomacromolecules date back decades, visible light has the unmistakable advantage of being considerably more biocompatible, and a spectrum of visible-light-driven methods is now available, chiefly for proteins and nucleic acids. This review will discuss modifications of native functional groups (FGs), including functionalization, labeling, and cross-linking techniques as well as the utility of oxidative degradation mediated by photochemically generated reactive oxygen species. Furthermore, transformations at non-native, bioorthogonal FGs on biomacromolecules will be addressed, including photoclick chemistry and DNA-encoded library synthesis as well as methods that allow manipulation of the activity of a biomacromolecule.

Visible-Light-Mediated Modification and Manipulation of Biomacromolecules.

The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

/pdf/light-induced-primary-amines-and-o-nitrobenzyl-alcohols-1vprgyl9s4.pdf

Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation.

Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in chemical modification and functional regulation of biomolecules. This review summarizes the developments and applications of the representative bioorthogonal reactions including the Staudinger reactions, the metal-mediated bioorthogonal reactions, the strain-promoted cycloadditions, the inverse electron demand Diels-Alder reactions, the light-triggered bioorthogonal reactions, and the reactions of chloroquinoxalines and ortho-dithiophenols.

Bioorthogonal Ligations and Cleavages in Chemical Biology.

Mass Spectrometry-Based Protein Complex Profiling in Time and Space.

Genetically Encoded Residue-Selective Photo-Crosslinker to Capture Protein-Protein Interactions in Living Cells

CuO nanoparticles (CuO NPs) are increasingly used in marine antifouling paints and as an antimicrobial antifouling agent in aquaculture industry, thus greatly increasing the probability of their release into the coastal aquaculture environments. With the wide application of CuO NPs, their potential environmental impact is currently highly topical focus of concern. In this study, the short term (7 days) and long term (35 days) effect of CuO NPs on the nitrogen transformation of sediment in the coastal aquaculture area were investigated. It was demonstrated that the addition of CuO NPs could lead to the increase in ammonium and decrease in nitrate concentration after a long-term exposure. Lactate dehydrogenase (LDA) release assays and NADH detection suggested that CuO NPs could significantly inhibit the viability of bacteria. Metagenomic results further indicated that CuO NPs could obviously impact the functional gene and metabolic enzymes related to nitrogen metabolic pathway and glycolysis pathway which confirmed the inhibitory impact of CuO NPs on nitrogen transformation. Overall, this study highlights the impact of CuO NPs on the nitrogen transformation in the sediment of coastal aquaculture area and reveals the release of CuO NPs should be controlled because of their potential for eutrophication. 

Comprehensive evaluation of the impact of CuO nanoparticles on nitrogen transformation in the coastal aquaculture area

Disclosing the ecological implications of heavy metal disturbance on the microbial N-transformation process in the ocean tidal flushing urban estuary

Exploring the variation of bacterial community and nitrogen transformation functional genes under the pressure of heavy metals in different coastal mariculture patterns.

Cai-Hu Wang

Papers

Genetically Encoded Residue-Selective Photo-Crosslinker to Capture Protein-Protein Interactions in Living Cells

Comprehensive evaluation of the impact of CuO nanoparticles on nitrogen transformation in the coastal aquaculture area

Disclosing the ecological implications of heavy metal disturbance on the microbial N-transformation process in the ocean tidal flushing urban estuary

Exploring the variation of bacterial community and nitrogen transformation functional genes under the pressure of heavy metals in different coastal mariculture patterns.

Molecular diversity and biogeography of benthic microeukaryotes in temperate seagrass (Zostera japonica) systems of northern China