• Issue

    ChemBioChem: Volume 23, Issue 24

    December 16, 2022

Cover Pictures

Free Access

Front Cover: pH-Responsive Self-Assembled Compartments as Tuneable Model Protocellular Membrane Systems (ChemBioChem 24/2022)

  • First Published: 10 November 2022
Description unavailable

The self-assembly behaviour of a pH-responsive amphiphile, mono-N-dodecyl phosphate (DDP) is illustrated on the front cover. As shown, they readily form vesicles over a very wide pH range by themselves, thereby providing a robust alternative to fatty acid-based protocellular systems. This feature also provides a respite from the constraints that limit the environments that would have been suitable for the emergence of protocells on the early Earth. Further, they result in robust vesicles when mixed with other single- and di-acyl chain derivatives. In all, the unique pH-responsive nature of DDP-based membranes highlights the advantages that these systems would have had for emergence of early functional cells and for the engineering of tuneable membranes with potential translational implications. [Designed by Ms. Tejal Vyas with critical scientific inputs from Dr. Chaitanya Mungi (Affiliation: Science Activity Centre at IISER Pune).] More information can be found in the Research Article by S. Sarkar, S. Rajamani et al.

Concepts

Selective Acylation of Proteins at Gly and Lys in His Tags

  • First Published: 19 August 2022
Description unavailable

Selective, autocatalytic acylation of Gly and Lys amines in poly-His sequences in peptides and proteins using new reagents based on phenyl esters provide stable conjugates. We have demonstrated the robustness of these methods by attaching different moieties such as azides, fluorophores, and biotin to different proteins, including antibodies.

Open Access

Synthetic Approaches to Break the Chemical Shift Degeneracy of Glycans

  • First Published: 25 August 2022
Description unavailable

NMR spectroscopy is the leading technique for structural characterization of glycans and elucidation of their interactions with proteins. Synthetic probes carrying isotopes or lanthanide tags represent elegant strategies to simplify the NMR analysis of the unlabeled analogues, contributing to the fundamental understanding of glycans.

Reviews

Very Important Paper

DNA-Mediated Control of Protein Function in Semi-Synthetic Systems

  • First Published: 04 September 2022
Description unavailable

The various strategies for interfacing DNA with proteins to control protein function in engineered semi-synthetic systems are discussed in this review. We highlight the main advances in the field, delineate the current limitations, and identify the areas that are in need of future development.

Research Articles

pH-Responsive Self-Assembled Compartments as Tuneable Model Protocellular Membrane Systems

  • First Published: 15 August 2022
Description unavailable

The self-assembly behaviour and membrane physicochemical properties of mono-N-dodecyl phosphate (DDP) were studied under different conditions. DDP formed vesicles in low concentration, over a wide range of pH. Physicochemical properties of DDP based membranes changed as a function of pH. Its tuneable nature and unique membrane properties, make it a very enticing model protocell membrane candidate.

Comparison of Different Competitive Proteome Profiling Approaches in Target Identification of Covalent Inhibitors

  • First Published: 22 October 2022
Description unavailable

Two competitive proteome profiling approaches were employed and compared in the identification of cellular targets of a covalent drug, afatinib, leading to the discovery of MYH9 as an off-target partner. Functional validation experiments have been carried out to validate this off-target.

Proline C−H Bonds as Loci for Proline Assembly via C−H/O Interactions

  • First Published: 21 September 2022
Description unavailable

C−H bonds of proline are particularly favorable sites for C−H/O interactions, including intermolecular assembly and intramolecular structure stabilization. These C−H/O interactions, which occur at all proline ring positions, exhibit short H⋅⋅⋅O distances, and are significantly stabilized by stereoelectronic effects, with only a minor electrostatic contribution in solution.

Open Access

Prebiotic Foam Environments to Oligomerize and Accumulate RNA

  • First Published: 10 November 2022
Description unavailable

Prebiotic foams are a new environment for the emergence of life. The wet-dry cycling at the enhanced interfacial area caused higher yields in catalyst-free RNA polymerization compared to an environment with low interfacial area. At the surfaces of air bubbles, we observed growth of DNA rich aggregates, which were able to fuse and detach to be accumulated at other bubbles.

Very Important Paper

Mimicking Natural Metabolisms: Cell-Free Flow Preparation of Dopamine

  • First Published: 31 October 2022
Description unavailable

Dopamine in-vivo metabolism was reproduced employing a combination of immobilized enzymes integrated in a flow chemistry reactor. A decarboxylase from Bacillus pumilis and a tyrosinase from Agaricus bisporus have been selected for their cofactor-independency. The efficient ex-vivo cascade allowed for dopamine biosynthesis with excellent yields (85 %) and rapid reaction times (45 min).

Antiviral Disaccharide Lead Compounds against SARS-CoV-2 through Computer-Aided High-Throughput Screen

  • First Published: 20 October 2022
Description unavailable

Antiviral mechanism of disaccharide lead compounds: Disaccharide lead compounds bind to the RBD structure of SARS-CoV-2/ SARS-CoV-2 Omicron variant spike protein, restraining their formation of a ternary complex with heparan sulfate (HS) and angiotensin-converting enzyme 2 (ACE2), thus inhibiting virus attachment to the cell surface.

Open Access

Optimization of RiPCA for the Live-Cell Detection of Pre-MicroRNA-Protein Interactions

  • First Published: 02 November 2022
Description unavailable

Interest in studying reported, but under-characterized RNA-protein interactions (RPI) warrants the development of tools to detect and validate these interactions. RiPCA is a cell-based assay capable of detecting pre-miRNA-protein interactions in a sequence-specific manner. This study reports the optimization of RiPCA and its application in detecting interactions between the RBPs hnRNP A1, Msi1, and Msi2 and select pre-miRNA binding partners.

Open Access

Enzymatic Generation of Double-Modified AdoMet Analogues and Their Application in Cascade Reactions with Different Methyltransferases

  • First Published: 26 October 2022
Description unavailable

An engineered MAT (methionine adenosyltransferase) is capable of generating double-modified AdoMet analogues (DM-AdoMets) when provided with non-natural methionine analogues and nucleoside-modified ATP analogues. DM-AdoMets have unique properties and not all MTases (methyltransferases) can easily convert them. This increases selectivity for MTase-based biomolecular labelling applications, enabling differential MTase targeting wherein multiple MTases are present (i. e., in cell).

Inverse In Vitro Selection Enables Comprehensive Analysis of Cross-Chiral L-Aptamer Interactions

  • First Published: 25 October 2022
Description unavailable

L-aptamers, those made of L-(deoxy)ribose nucleic acids, are a promising class of RNA affinity reagent, but their selectivity remains poorly characterized. Herein, we developed an “inverse” in vitro selection method that enables comprehensive analysis of L-aptamer selectivity and revealed promiscuous RNA-binding behaviors for a model L-aptamer.

Very Important Paper

Open Access

The Osteosarcoma Stem Cell Activity of a Gallium(III)-Phenanthroline Complex Appended to Salicylate

  • First Published: 25 October 2022
Description unavailable

Osteosarcoma is the most commonly diagnosed primary bone cancer and has strikingly low survival rates. Here we report the anti-osteosarcoma properties of a six-coordinate gallium(III) complex with two polypridyl ligands and salicylate, a non-steroidal anti-inflammatory drug. The gallium(III) complex kills bulk osteosarcoma cells and osteosarcoma stem cells in the micromolar range by evoking apoptosis through DNA damage and cyclooxygenase-2 downregulation.

Open Access

Synthetic Studies with Bacitracin A and Preparation of Analogues Containing Alternative Zinc Binding Groups

  • First Published: 26 October 2022
Description unavailable

An improved synthetic route is reported for the clinically used natural product antibiotic bacitracin A. This new route provides access to the bacitracin scaffold with confidence in the stereochemical purity of the product and enables studies involving structural variation of the bacitracin framework.

Effects of Charged Lipids on Giant Unilamellar Vesicle Fusion and Inner Content Mixing via Freeze-Thawing

  • First Published: 02 November 2022
Description unavailable

Liposomes prepared with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and negatively charged phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)) showed a greater ratio of inner content mixing by freeze-thawing (F/T) with a lower rate of rupture, while liposomes with POPC and positively charged phospholipids (1,2-dioleoyl-3-trimethylammonium-propane) showed a greater ratio of rupture. These findings could be useful for providing an improved artificial model.

Open Access

Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis

  • First Published: 03 November 2022
Description unavailable

How the magic begins: The l-tryptophan decarboxylase PsiD initiates the biosynthesis of the psychotropic natural product psilocybin in Psilocybe mushrooms. Its in vitro biochemical characterization and in silico modeling of its structure identified a non-canonical serine protease triad for autocatalytic cleavage of the proenzyme. PsiD's substrate flexibility makes it a versatile catalyst for biotechnological applications.

Dioxetane Derivative Containing Carboxy Group as a Chemiluminophore-Introducing Reagent

  • First Published: 26 October 2022
Description unavailable

A novel carboxy group-containing chemiluminophore derivative, which enabled the simple introduction of a chemiluminophore to the molecule of interest, was developed. This chemiluminophore cast luminescence light without enzymes, such as luciferase. Chemiluminophore-containing probes thus obtained could be visualized by in vivo imaging system.

Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis

  • First Published: 24 October 2022
Description unavailable

The crystal structures of CmnG-A, which activates a nonproteinogenic amino acid l-Cap, provide insights into the specificity and engineering opportunities of adenylation domains.

Open Access

A Comparative Study of Nitroxide-Based Biradicals for Dynamic Nuclear Polarization in Cellular Environments

  • First Published: 17 October 2022
Description unavailable

Nitroxide-based biradicals are increasingly being used as polarization agents for sensitivity-enhanced NMR spectroscopy in cells. They are, however, susceptible to reduction in the cellular environment. Here, we evaluate the stability of three popular polarization agents, AMUPol, AsymPolPOK, and TOTAPOL in cellular lysates, and introduce a new polarization agent, POPAPOL, which exhibits improved properties under reducing conditions.