Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications

The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pKR+ rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pKR+ values ionise and desorb better. Trityl blocks were synthesised that have high pKR+ values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. 13C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine

Uridine 2′‐Carbamates: Facile Tools for Oligonucleotide 2′‐Functionalization

A facile method for preparation of uridine 2′‐carbamate derivatives based on reaction of 3′,5′‐disilyl‐protected uridine with 1,1′‐carbonyldiimidazole followed by treatment with an aliphatic amine is presented. A phosphoramidite monomer suitable for automated oligonucleotide synthesis is obtained in a few steps. The compounds are useful for the introduction of various labels and modifications into an oligonucleotide chain. Although 2′‐carbamate modification is somewhat destabilizing for DNA‐DNA and DNA‐RNA duplexes, it is suitable for the direction of ligands into the minor groove of duplexes or at non‐base‐paired sites (e.g., loops and bulges) of oligonucleotides. Pyrene‐modified oligonucleotide 2′‐carbamates show a considerable increase in fluorescence intensity upon hybridization to a complementary RNA (but not DNA).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153179/1/cpnc0421.pd

Chemical Elicitors of Antibiotic Biosynthesis in Actinomycetes

Whole genome sequencing of actinomycetes has uncovered a new immense realm of microbial chemistry and biology. Most biosynthetic gene clusters present in genomes were found to remain “silent” under standard cultivation conditions. Some small molecules—chemical elicitors—can be used to induce the biosynthesis of antibiotics in actinobacteria and to expand the chemical diversity of secondary metabolites. Here, we outline a brief account of the basic principles of the search for regulators of this type and their application

Sensing of Antibiotic–Bacteria Interactions

Sensing of antibiotic–bacteria interactions is an important area of research that has gained significant attention in recent years. Antibiotic resistance is a major public health concern, and it is essential to develop new strategies for detecting and monitoring bacterial responses to antibiotics in order to maintain effective antibiotic development and antibacterial treatment. This review summarizes recent advances in sensing strategies for antibiotic–bacteria interactions, which are divided into two main parts: studies on the mechanism of action for sensitive bacteria and interrogation of the defense mechanisms for resistant ones. In conclusion, this review provides an overview of the present research landscape concerning antibiotic–bacteria interactions, emphasizing the potential for method adaptation and the integration of machine learning techniques in data analysis, which could potentially lead to a transformative impact on mechanistic studies within the field

Imaging-based profiling for elucidation of antibacterial mechanisms of action

In this review, we aim to summarize experimental data and approaches to identifying cellular targets or mechanisms of action of antibacterials based on imaging techniques. Imaging-based profiling methods such as bacterial cytological profiling, dynamic bacterial morphology imaging and others have become a useful research tool for mechanistic studies of new antibiotics as well as combinations with conventional ones and other therapeutic options. The main methodological, experimental details and obtained results are summarized and discussed. The review covers the literature up to Feb 2024

Introduction of Carbonyl Groups into Antibodies

Antibodies and their derivatives (scFv, Fabs, etc.) represent a unique class of biomolecules that combine selectivity with the ability to target drug delivery. Currently, one of the most promising endeavors in this field is the development of molecular diagnostic tools and antibody-based therapeutic agents, including antibody–drug conjugates (ADCs). To meet this challenge, it is imperative to advance methods for modifying antibodies. A particularly promising strategy involves the introduction of carbonyl groups into the antibody that are amenable to further modification by biorthogonal reactions, namely aliphatic, aromatic, and α-oxo aldehydes, as well as aliphatic and aryl–alkyl ketones. In this review, we summarize the preparation methods and applications of site-specific antibody conjugates that are synthesized using this approach

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs

Fluorescence of BODIPY Dyes in Gas Phase at near Ambient Conditions

Molecular fluorescence is a phenomenon that is usually observed in condensed phase. It is strongly affected by molecular interactions. The study of fluorescence spectra in the gas phase can provide a nearly-ideal model for the evaluation of intrinsic properties of the fluorophores. Unfortunately, most conventional fluorophores are not volatile enough to allow study of their fluorescence in the gas phase. Here we report very bright gas phase fluorescence of simple BODIPY dyes that can be readily observed at atmospheric pressure using conventional fluorescence instrumentation. To our knowledge, this is the first example of visible range gas phase fluorescence at near ambient conditions. Evaporation of the dye in vacuum allowed us to demonstrate organic molecular electroluminescence in gas discharge excited by electric field produced by a Tesla coil