scholarly journals Targeted Activation in Localized Protein Environments via Deep Red Photoredox Catalysis

Author(s):  
Nicholas Tay ◽  
Keun Ah Ryu ◽  
John Weber ◽  
Aleksandra Olow ◽  
David Reichman ◽  
...  

State-of-the art photoactivation strategies in chemical biology provide spatiotemporal control and visualization of biological processes. However, using high energy light (λ < 500 nm) for substrate or photocatalyst sensitization can lead to background activation of photoactive small molecule probes and reduce its efficacy in complex biological environments. Here we describe the development of targeted aryl azide activation via deep red light (λ = 660 nm) photoredox catalysis and its use in photocatalyzed proximity labeling. We demonstrate that aryl azides are converted to triplet nitrenes via a novel redox-centric mechanism and show that its spatially localized-formation requires both red light and a photocatalyst-targeting modality. This technology was applied in different colon cancer cell systems for targeted protein environment labeling of epithelial cell adhesion molecule (EpCAM). We identified a small subset of proteins with previously known and unknown association to EpCAM, including CDH3, a clinically relevant protein that shares high tumor selective expression with EpCAM.

2021 ◽  
Author(s):  
Cristina Parisi ◽  
Mariacristina Failla ◽  
Aurore Fraix ◽  
Luca Menilli ◽  
Francesca Moret ◽  
...  

The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as “unconventional” therapeutics with precise spatiotemporal control by using light stimuli may open entirely new horizons for innovative...


2019 ◽  
Author(s):  
Elham Ahmadzadeh ◽  
N. Sumru Bayin ◽  
Xinli Qu ◽  
Aditi Singh ◽  
Linda Madisen ◽  
...  

AbstractThanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.Summary statementAhmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.


2015 ◽  
Vol 17 (41) ◽  
pp. 27380-27390 ◽  
Author(s):  
Sven H. C. Askes ◽  
Miroslav Kloz ◽  
Gilles Bruylants ◽  
John T. M. Kennis ◽  
Sylvestre Bonnet

Three molecules in a single lipid bilayer to trigger high-energy photochemistry with low-energy photons.


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1478 ◽  
Author(s):  
Monilola A. Olayioye ◽  
Bettina Noll ◽  
Angelika Hausser

As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo- and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.


1966 ◽  
Vol 44 (5) ◽  
pp. 663-668 ◽  
Author(s):  
W. B. Collins

The effects of different ratios of red to far-red radiation in continuous light on flower initiation in strawberry are described. A correlation was found between flower promotion and the content of far-red light in the supplied radiation which may be related to the red/far-red ratio of light and therefore to the level of phytochrome-Pfr in the plants. However, since relatively high energy (white) light was the only radiation used, a clear distinction between photosynthetic and red/far-red photoreversible effects is not possible. Flowering did not occur on all runner plants. Where flowering was promoted it invariably occurred first on the second- or third-formed runner plants on the stolon. Flowering was delayed on the proximal runner plants and never occurred on the mother plants. The results support the premise that a flower-inhibiting system was present along a concentration gradient in the runner.


2017 ◽  
Vol 45 (1) ◽  
pp. 275-285 ◽  
Author(s):  
Mingzi M. Zhang ◽  
Howard C. Hang

Reversible protein S-palmitoylation confers spatiotemporal control of protein function by modulating protein stability, trafficking and activity, as well as protein–protein and membrane–protein associations. Enabled by technological advances, global studies revealed S-palmitoylation to be an important and pervasive posttranslational modification in eukaryotes with the potential to coordinate diverse biological processes as cells transition from one state to another. Here, we review the strategies and tools to analyze in vivo protein palmitoylation and interrogate the functions of the enzymes that put on and take off palmitate from proteins. We also highlight palmitoyl proteins and palmitoylation-related enzymes that are associated with cellular differentiation and/or tissue development in yeasts, protozoa, mammals, plants and other model eukaryotes.


2021 ◽  
Author(s):  
Alicia E. Mangubat-Medina ◽  
Zachary T. Ball

Photocaging groups provide spatiotemporal control of function. This review surveys approaches to the design and synthesis of photocaged peptides and proteins, and provides an overview of the ways in which these tools have been applied to answer biological questions.


Processes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 680
Author(s):  
Jianyang Jiang ◽  
Xiong Xiong Liu ◽  
Jiayu Han ◽  
Ke Hu ◽  
Jun Song Chen

Transition metal hydroxides have attracted a lot of attention as the electrode materials for supercapacitors owing to their relatively high theoretical capacity, low cost, and facile preparation methods. However, their low intrinsic conductivity deteriorates their high-rate performance and cycling stability. Here, self-supported sheets-on-wire CuO@Ni(OH)2/Zn(OH)2 (CuO@NiZn) composite nanowire arrays were successfully grown on copper foam. The CuO nanowire backbone provided enhanced structural stability and a highly efficient electron-conducting pathway from the active hydroxide nanosheets to the current collector. The resulting CuO@NiZn as the battery-type electrode for supercapacitor application delivered a high capacity of 306.2 mAh g−1 at a current density of 0.8 A g−1 and a very stable capacity of 195.1 mAh g−1 at 4 A g−1 for 10,000 charge–discharge cycles. Furthermore, a quasi-solid-state hybrid supercapacitor (qss HSC) was assembled with active carbon, exhibiting 125.3 mAh g−1 at 0.8 A g−1 and a capacity of 41.6 mAh g−1 at 4 A g−1 for 5000 charge–discharge cycles. Furthermore, the qss HSC was able to deliver a high energy density of about 116.0 Wh kg−1. Even at the highest power density of 7.8 kW kg−1, an energy density of 20.5 Wh kg−1 could still be obtained. Finally, 14 red light-emitting diodes were lit up by a single qss HSC at different bending states, showing good potential for flexible energy storage applications.


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