Triggering biological processes: methods and applications of photocaged peptides and proteins

2021 ◽  
Author(s):  
Alicia E. Mangubat-Medina ◽  
Zachary T. Ball
Keyword(s):  
Biological Processes ◽  
Design And Synthesis ◽  
Spatiotemporal Control

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.

scholarly journals A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression

2019 ◽  
Author(s):  
Elham Ahmadzadeh ◽  
N. Sumru Bayin ◽  
Xinli Qu ◽  
Aditi Singh ◽  
Linda Madisen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Biological Processes ◽  
Control Of Gene Expression ◽  
A Cell ◽  
Summary Statement ◽  
Spatiotemporal Control ◽  
Mouse Lines

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.

scholarly journals Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1478 ◽  
Author(s):  
Monilola A. Olayioye ◽  
Bettina Noll ◽  
Angelika Hausser
Keyword(s):  
Membrane Trafficking ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Proteins ◽  
Biological Processes ◽  
Intracellular Membrane ◽  
Master Regulators ◽  
Cytoskeletal Remodeling ◽  
Wide Range ◽  
Spatiotemporal Control

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.

scholarly journals MICRO-OPTOMECHANICAL MOVEMENTS (MOMs) WITH SOFT OXOMETALATES (SOMs): CONTROLLED MOTION OF SINGLE SOFT OXOMETALATE PEAPODS USING EXOTIC OPTICAL POTENTIALS

2014 ◽  
Vol 02 (01) ◽  
pp. 1440006 ◽  
Author(s):  
BASUDEV ROY ◽  
NIRMALYA GHOSH ◽  
PRASANTA K. PANIGRAHI ◽  
AYAN BANERJEE ◽  
ATHARVA SAHASRABUDHE ◽  
...  
Keyword(s):  
Optical Trap ◽  
Stratified Medium ◽  
Biological Processes ◽  
Molecular Precursors ◽  
Design And Synthesis ◽  
Optical Potentials ◽  
Wide Range ◽  
Linearly Polarized ◽  
Important Challenge ◽  
Controlled Motion

An important challenge in the field of materials design and synthesis is to deliberately design mesoscopic objects starting from well-defined precursors and inducing directed movements in them to emulate biological processes. Recently, mesoscopic metal-oxide-based soft oxometalates (SOMs) have been synthesized from well-defined molecular precursors transcending the regime of translational periodicity. Here, we show that it is actually possible to controllably move such an asymmetric SOM, with the shape of a "peapod" along complex paths using tailor-made sophisticated optical potentials created by spin–orbit interaction of light due to a tightly focused linearly polarized Gaussian beam propagating through a stratified medium in an optical trap. We demonstrate motion of individual trapped SOMs along circular paths of more than 15 μm in a perfectly controlled manner by simply varying the input polarization of the trapping laser. Such controlled motion can have a wide range of applications starting from catalysis to the construction of dynamic mesoscopic architectures.

scholarly journals Protein S-palmitoylation in cellular differentiation

2017 ◽  
Vol 45 (1) ◽  
pp. 275-285 ◽  
Author(s):  
Mingzi M. Zhang ◽  
Howard C. Hang
Keyword(s):  
Posttranslational Modification ◽  
Protein Function ◽  
Cellular Differentiation ◽  
Protein S ◽  
Biological Processes ◽  
Global Studies ◽  
Technological Advances ◽  
Protein Palmitoylation ◽  
Spatiotemporal Control

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.

scholarly journals Design and Synthesis of Amino Acid Derivatives of Substituted Benzimidazoles and Pyrazoles as Selective Sirt1 Inhibitors

2020 ◽  
Author(s):  
Nikil Purushotham ◽  
Mrityunjay Singh ◽  
Bugga Paramesha ◽  
Vasantha Kumar ◽  
Sharad Wakode ◽  
...  
Keyword(s):  
Cancer Therapeutics ◽  
Breast Cancer Cell Lines ◽  
Biological Processes ◽  
Potential Therapeutic Target ◽  
Design And Synthesis ◽  
Acetylation Status ◽  
Interaction Map ◽  
Dynamics Simulations ◽  
Derivatives Of

Owing to its presence in several biological processes Sirt1 served as a potential therapeutic target for many diseases. Here we report the synthesis of two distinct series of novel Sirt1 selective inhibitors, benzimidazole monopeptides and 5-pyrazolyl methylidene rhodanine carboxylic acid derived amino acids, constructed using structure-guided computational approaches. Furthermore, compounds were evaluated, against human Sirt1-3 for <i>in-vitro</i> inhibitory activity compared to Ex527 (reported Sirt1-selective inhibitor), in liver and breast cancer cell lines for cytotoxicity. The tryptophan conjugates 13h (IC<sub>50</sub> = 0.66 µM) and 7d (IC<sub>50</sub> = 0.77 µM) demonstrated maximum efficacy to inhibit Sirt1. Molecular dynamics simulations unveil the interaction map and electrostatic complementarity at substrate binding site, could be a cause of selective Sirt1 inhibition.<b> </b>Furthermore, the Sirt1 inhibition was<b> </b>monitored via<b> </b>increased p53 acetylation status checked in HepG2 cells. These findings will pave the pathway for developing novel selective Sirt1-inhibitors in cancer therapeutics.

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

2021 ◽  
Author(s):  
Nicholas Tay ◽  
Keun Ah Ryu ◽  
John Weber ◽  
Aleksandra Olow ◽  
David Reichman ◽  
...  
Keyword(s):  
Cell Adhesion Molecule ◽  
Red Light ◽  
High Energy ◽  
Small Subset ◽  
Biological Processes ◽  
Photoredox Catalysis ◽  
Aryl Azides ◽  
Small Molecule Probes ◽  
Spatiotemporal Control ◽  
Protein Environment

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.

scholarly journals Sensing Performance and Efficiency of Two Energy Transfer-Based Two-Photon Fluorescent Probes for pH

Sensors ◽  
2018 ◽  
Vol 18 (12) ◽  
pp. 4407
Author(s):  
Yujin Zhang ◽  
Wei Hu
Keyword(s):  
Energy Transfer ◽  
Fluorescent Probes ◽  
Energy Transfer Process ◽  
Energy Transfer Efficiency ◽  
Photon Absorption ◽  
Biological Processes ◽  
Two Photon Absorption ◽  
Design And Synthesis ◽  
Two Photon ◽  
Ph Values

The design and synthesis of fluorescent probes for monitoring pH values inside living cells have attracted great attention, due to the important role pH plays in many biological processes. In this study, the optical properties of two different two-photon fluorescent probes for pH are studied. The ratiometric sensing of the probes are theoretically illustrated. Meanwhile, the recognitional mechanisms of the probes are investigated, which shows the energy transfer process when react with H+. Specially, the calculated results demonstrate that Probe1 possesses a higher energy transfer efficiency and a larger two-photon absorption cross-section than Probe2, indicating it to be a preferable pH fluorescent probe. Therefore, the influence of connection between the donor and the acceptor on the sensing performances of the probe is demonstrated. Our results help to understand the experimental observations and provide a theoretical basis to synthesize efficient two-photon fluorescent probes for monitoring pH changes.

scholarly journals Design and Synthesis of Amino Acid Derivatives of Substituted Benzimidazoles and Pyrazoles as Selective Sirt1 Inhibitors

2020 ◽  
Author(s):  
Nikil Purushotham ◽  
Mrityunjay Singh ◽  
Bugga Paramesha ◽  
Vasantha Kumar ◽  
Sharad Wakode ◽  
...  
Keyword(s):  
Cancer Therapeutics ◽  
Breast Cancer Cell Lines ◽  
Biological Processes ◽  
Potential Therapeutic Target ◽  
Design And Synthesis ◽  
Acetylation Status ◽  
Interaction Map ◽  
Dynamics Simulations ◽  
Derivatives Of

Owing to its presence in several biological processes Sirt1 served as a potential therapeutic target for many diseases. Here we report the synthesis of two distinct series of novel Sirt1 selective inhibitors, benzimidazole monopeptides and 5-pyrazolyl methylidene rhodanine carboxylic acid derived amino acids, constructed using structure-guided computational approaches. Furthermore, compounds were evaluated, against human Sirt1-3 for <i>in-vitro</i> inhibitory activity compared to Ex527 (reported Sirt1-selective inhibitor), in liver and breast cancer cell lines for cytotoxicity. The tryptophan conjugates 13h (IC<sub>50</sub> = 0.66 µM) and 7d (IC<sub>50</sub> = 0.77 µM) demonstrated maximum efficacy to inhibit Sirt1. Molecular dynamics simulations unveil the interaction map and electrostatic complementarity at substrate binding site, could be a cause of selective Sirt1 inhibition.<b> </b>Furthermore, the Sirt1 inhibition was<b> </b>monitored via<b> </b>increased p53 acetylation status checked in HepG2 cells. These findings will pave the pathway for developing novel selective Sirt1-inhibitors in cancer therapeutics.

scholarly journals Photo-controllable bioorthogonal chemistry for spatiotemporal control of bio-targets in living systems

2020 ◽  
Vol 11 (13) ◽  
pp. 3390-3396 ◽  
Author(s):  
Jinbo Li ◽  
Hao Kong ◽  
Chenghong Zhu ◽  
Yan Zhang
Keyword(s):  
Chemical Biology ◽  
Living Systems ◽  
Biological Processes ◽  
Bioorthogonal Chemistry ◽  
Spatiotemporal Control

The establishment of photo-controllable bioorthogonal chemistry is one of the most significant advances in chemical biology to perturb and study biological processes.

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