Steroid compounds are important messengers in the human body that can be described using multiple nomenclature systems, each reflecting a different perspective on structure or function. Chemical nomenclature, based on IUPAC conventions, classifies steroids according to their ring structure and functional groups, whereas functional nomenclature reflects a compound's source, biological action, regulatory pathways, metabolism, or clinical application. These parallel systems are often applied inconsistently across disciplines, leading to ambiguity in interpretation and communication. This review outlines the foundations of chemical and functional naming, highlights circumstances in which nomenclature becomes inconsistent, and illustrates how physiology, molecular biology, receptor diversification, genetics, oncology, and the microbiome complicate terminology. Because clinicians, biochemists, pharmacologists, and researchers often apply different naming logics, coherent definitions and consistent usage are necessary for clear scientific discourse. This review proposes considerations to support more precise application of steroid nomenclature in academic publications.
Berberis turcomanica, commonly known as the Turcoman Barberry, is a lesser-studied deciduous shrub of the Berberidaceae family, primarily distributed in Central Asia with its heartland in Turkmenistan. The extracts of the berries of Berberis turcomanica (BTB) were subjected to in vitro assays to assess antioxidant capacity (DPPH, ABTS, FRAP, CUPRAC), enzyme inhibitory activities (acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase), antimicrobial potential (against selected bacterial and fungal strains), and cytotoxic effects on human HaCaT cell lines. Among the 28 chemical constituents analyzed using UHPLC-DAD-QqQ-MS/MS. The extracts exhibited strong antioxidant activity, supported by high total phenolic and flavonoid contents. Significant enzyme inhibition, particularly against tyrosinase and α-glucosidase, suggests potential applications in managing hyperpigmentation and diabetes. Both fruit extracts also exhibited promising antibacterial effects against several bacterial strains and moderate antifungal activity; however, the extracts demonstrated low cytotoxicity toward non-cancerous human keratinocyte HaCaT cells, with IC50 values exceeding 400 µg mL-1, indicating a favorable safety profile and good biocompatibility under the tested conditions. Molecular docking, MD simulation-based analyses, and DFT calculations provided supportive insights into the potential activities of selected individual compounds identified in the extracts, partially complementing the experimentally obtained findings. These results present the first detailed pharmacological and chemical investigation of B. turcmanica berries in two extraction methods and support their potential use as a multifunctional natural agent in pharmaceutical and nutraceutical applications.
Peptides have evolved from naturally occurring ligands and classical hormones into a versatile and engineerable class of functional molecules. This review provides a comprehensive overview of the technological advances that collectively enable programmable peptide engineering across the entire discovery-to-development pipeline. We first discuss innovations in automated flow synthesis, chemoselective ligation, noncanonical residue incorporation, backbone editing, conformational constraint, and late-stage functionalization that have transformed peptide chemistry from linear sequence assembly into a modular engineering scaffold. We then examine modern discovery approaches, including phage display and mRNA display with the RaPID system, along with computational and AI-enabled design strategies that accelerate hit identification and multi-parameter optimization. Biophysical characterization techniques, cellular target engagement assays, and emerging delivery strategies are also reviewed as critical tools for bridging biochemical potency with intracellular activity. Finally, we discuss the translational barriers facing peptide therapeutics and the engineering strategies that have enabled successful clinical applications. Together, these advances establish a new era in which peptides are no longer viewed as inherently labile biomolecules but as chemically programmable scaffolds whose structures and functions can be precisely engineered.
Propolis exhibits a wide range of biological properties, including antimicrobial, anti-inflammatory, anti-allergic, antioxidant, anticancer, antitumour and antigenotoxic effects. It mostly contains flavonoids and phenolic compounds. Since propolis is used for therapeutic purposes, its effects should be investigated in detail. This study aims to evaluate the potential genotoxic and antigenotoxic effects of water-based organic Turkish propolis using the Hen's Egg Test for Micronucleus Induction (HET-MN), as well as its chemical composition (by HPLC-DAD). Three different doses (500 µg per egg, 250 µg per egg and 50 µg per egg) of propolis were injected into fertilized chicken eggs at incubation day 8 to determine genotoxic effects. Cyclophosphamide (50 µg per egg) was used as genotoxic agent. In addition, propolis doses were administered together with cyclophosphamide to determine the antigenotoxic effect. Ascorbic acid (50 µg per egg) was used as antigenotoxic agent. Embryonic peripheral blood smears were prepared and stained on 11th day of incubation. The frequencies of micronucleus and nuclear abnormalities in erythrocytes were determined using light microscopy. According to the statistical analysis, water-based organic Turkish propolis did not show any genotoxic effect at the three tested doses. However, only the lowest dose of the propolis showed antigenotoxic effect. In addition, embryos were macroscopically examined for teratogenicity. To evaluate bone development, some embryos were stained with Alizarin Red S, and no teratogenic effects or delays in bone development were observed. Nevertheless, all three propolis doses caused significant decreases in both the number of live embryos and relative embryo weight. HPLC-DAD analysis revealed that benzoic acid was the main component (272.5 µg ml-1), followed by caffeic acid (265.4 µg ml-1) and ferulic acid (53.8 µg ml-1). While the anti-genotoxic effect of low doses of propolis may be attributed to its high antioxidant content, its effect on reducing embryo weight at high doses may be related to its high caffeic acid content. Our findings suggest that low doses of propolis are relatively safe, whereas exposure to high doses could pose potential risks.
[This corrects the article DOI: 10.1039/D5RA07856C.].
Sulfur(vi) fluoride exchange (SuFEx) reactions were introduced as next-generation click transformations that form robust sulfur(vi)-based linkages under mild conditions. Their defining feature is the unusual behaviour of the S-F bond: it is thermodynamically stable, yet can be selectively substituted when a suitable nucleophile is properly positioned. This balance has made SuFEx a valuable platform in chemical biology, enabling novel covalent probes, inhibitors and conjugation strategies in complex aqueous environments. In contrast, SuFEx applications to nucleosides, nucleotides and nucleic acids remain comparatively scarce and are only now beginning to mature. Progress has been limited by scaffold-specific synthetic and workflow constraints, including the scarcity of broadly enabling methodological studies and limited compatibility with standard oligonucleotide workflows. Even so, recent reports show that these barriers can be overcome in selected settings and that SuFEx can be translated into functional nucleic-acid constructs. This review summarises current advances with a focus on concepts and practical design rules. The first part is chemistry-centered: it compares the most successful strategies for installing sulfur(vi)-fluoride electrophiles on nucleoside, nucleotide, and oligonucleotide frameworks, and discusses reagent choices, linker designs and warhead positioning. The second part focuses on applications, outlining how these synthetic advances are turned into chemical biology tools where proximity effects convert reversible recognition into durable capture. We conclude by highlighting key bottlenecks and the most promising opportunities for progress.
Lung cancer remains the leading cause of both cancer incidence and mortality worldwide, rendering it a primary focus in oncology research. This pressing global health challenge has created an urgent demand for novel therapeutic agents with high efficacy and low toxicity. Owing to their distinctive chemical structures and wide range of biological activities, natural products have become essential resources in the development of medicines. Alepterolic acid is a natural diterpenoid from the plant Aleuritopteris argentea (Gmél.) Fée, a fern used in folk medicine in China. In this study, a total of 31 derivatives were gained by the incorporation of urea and piperazine groups into alepterolic acid. Among them, the inhibition rate of 21 compounds against A549 cells exceeded 50% at 10 μM. Specifically, the IC50 values of compounds 15o and 15u against A549 cells were 1.8 ± 0.3 and 1.5 ± 0.2 μM, respectively. Moreover, it was found that the proliferation and migration of A549 cells were inhibited remarkably by both compounds 15o and 15u as the cell cycle was arrested at the G1 phase. At the molecular level, compounds 15o and 15u exhibited the ability to induce cleavage and activation of caspase-3 and caspase-9, promote PARP-1 cleavage, downregulate Bcl-2 expression, and upregulate Bax protein levels. The docking simulation results suggested that compounds 15o and 15u could stably bind to caspase-3, Bax, Bcl-2, caspase-9, and PARP-1. The physicochemical property/ADMET evaluation demonstrated that the physicochemical characteristics of compound 15o were indicative of an enhanced bioavailability. To sum up, urea- and piperazine-functionalized alepterolic acid derivatives possess significant anti-cancer activities and are worthy of further research.
DNA origami has emerged as a versatile platform for constructing nanoscale architectures with precise shape programmability, molecular-level addressability, and dynamic structural reconfigurability. Since its introduction, DNA origami has evolved from a structural design method into a functional nanosystem capable of integrating molecular recognition, logic-gated operations, and mechanical motion, enabling a wide range of biomedical applications. This review outlines recent advances in DNA origami-based drug delivery and the regulation of cellular functions and cell fate. Strategic control over size, shape, and mechanical properties is discussed in the context of cellular uptake, intracellular behavior, and the efficient delivery of small-molecule drugs and nucleic acid therapeutics. Recent progress in dynamic DNA origami nanodevices and nanorobots that respond to molecular, chemical, or physical cues is highlighted, including systems that enable spatiotemporally controlled payload release and the nanoscale organization of membrane receptors to modulate cellular signaling. In addition, key stabilization strategies required for in vivo applications, such as covalent linking of constituent DNA strands and surface-coating methods, are summarized. Finally, future challenges and perspectives are discussed, emphasizing the growing role of chemical biology in endowing DNA origami with sensing, decision-making, and adaptive functions for intelligent nanomedicine.
Novel biodosimetry assays are needed for potential radiological incidents to rapidly assess radiation exposure and guide medical treatments. Mass spectrometry-based metabolomic analysis using a sorptive phase extraction is a rapid and efficient method for radiation-induced biomarkers in biofluids. Here, we developed a chemically functionalized polymeric Sorbent Phase Sorptive Extraction (SPSE) method. This method employs polymeric thin film sorbents with tailored organic functional groups, which directly bind radiation-responsive biomolecules and increase sample absorption capacity. This microporous membrane system enables rapid, high-sensitivity extraction of metabolites spanning a wide polarity range from urine, serum, and whole blood. We characterized the surface morphology, chemical functionality, and hydrophilicity of multiple sorbent-coated cellulose membranes, including plasma-functionalized nylon-6. Matrix interference was evaluated using untargeted metabolomics, and analytical performance was assessed using a targeted multiplex radiation biomarker panel. Urine, serum, and whole blood were collected from male and female C57BL/6 mice (9 weeks old) exposed to X-rays at 1 day (0, 2, 8, 13 Gy) and 7 days (0, 2, 8 Gy) post-irradiation. The membrane types preserve metabolite stability at room temperature for up to two weeks; however, nylon-6-based cellulose paper membranes exhibited the highest surface porosity, absorption capacity, and metabolite recovery. Classifier performance evaluated using receiver operating characteristic analysis demonstrated comparable sensitivity and specificity between SPSE and conventional dilute-and-shoot workflows. Collectively, these results support further development of polymeric sorbent coated paper and fabric-based substrates to increase throughput while eliminating cold-chain requirements. These environmentally conscious design features exemplify principles of green chemistry including lowering chemical waste and operational energy demand.
Carbocyclic nicotinamide cofactors are attractive NAD(P)+ analogues that retain native redox activity while offering substantially enhanced chemical and thermal stability. Their broader use, however, has been limited by demanding multistep chemical syntheses involving complex protection strategies and limited exploration of enzymatic alternatives. In this study, we studied both chemical and enzymatic approaches for the synthesis of carba-analogues. For the enzymatic route, we identify and characterize the key enzymes involved in cofactor assembly, evaluating their tolerance toward non-native, carbocyclic substrates and extending the assembly to further generate the phosphorylated analogue, cNADP+. In addition, extending the analysis to cofactor thermostability, carba-NAD+ displayed a remarkable halftime (t 1/2 > 1386 h at 50 °C), far exceeding that of NAD+ (t 1/2 = 76 h) and is accepted by a broad panel of oxidoreductases. Collectively, this work outlines a modular workflow and details the synthesis landscape for accessing thermostable, synthetic nicotinamide cofactor analogues, cNAD+ and cNADP+, unveiling new opportunities for their application in cofactor engineering and synthetic biocatalysis.
Antimicrobial peptides (AMPs) are central components of the innate immunity system that can be found in almost all living organisms. They are promising alternatives to conventional antibiotics due to their broad-spectrum activity and reduced susceptibility to resistance. Experimental studies have shown that combinations of AMPs can act synergistically, achieving enhanced antibacterial efficacy at lower total concentrations in combination than individually. However, despite its prevalence, AMP synergy has until recently been lacking a unifying mechanistic and predictive framework. In this review, we combine the latest theoretical, computational, and experimental advances to present a novel quantitative framework that views AMP synergy as a consequence of cooperative membrane association. Chemical-kinetic models of AMPs association to bacterial membranes show that favorable intermolecular interactions between different AMP species accelerate their binding, enhancing antibacterial activity. Within this framework, an effective interaction parameter, ΔE, emerges as a quantitative descriptor of cooperativity linking microscopic interactions to macroscopic synergy metrics such as minimal inhibitory concentrations (MIC). Extensions of this approach rationalize the enhanced efficacy of heterogeneous multi-AMP mixtures and clarify the specific case of AMPs associating to each other as hetero-oligomers before binding to the bacterial membranes. Complementary statistical and machine-learning analyses further demonstrate that synergistic AMP combinations are characterized by physicochemical complementarity rather than similarity, enabling prediction of synergy from sequence-derived features. The review demonstrates that AMP synergy can be quantitatively described and potentially rationally designed using a combined chemical-kinetic and statistical machine-learning approach, providing a foundation for systematic development of effective and resistance-resilient multi-AMP therapeutics.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway is a crucial modulator of innate immunity and an important target for next-generation cancer immunotherapy. Numerous cGAS-STING agonists have been developed and evaluated for their ability to promote anti-tumour immune responses. Cyclic dinucleotides (CDNs) are the most widely employed natural STING agonists; however, poor membrane permeability and enzymatic instability have motivated the development of non-CDN small-molecule agonists, including organic scaffolds and metal-based complexes with improved stability and tunable physicochemical properties. Additionally, nanomaterials that incorporate metal complexes with or without STING agonists have recently emerged as promising platforms for achieving robust therapeutic effects, facilitating targeted delivery, controlled release, and integration with other treatment modalities such as photodynamic therapy. This review offers a comprehensive examination of advancements over the past two years in the design and development of STING modulators, including organic scaffolds, metal-based complexes, and nanomaterials that encapsulate or tether metal-based drugs. It emphasises their chemical structures and the molecular mechanisms that facilitate STING activation and discusses significant challenges while delineating future research and therapeutic development directions.
Synthetic biology enables the creation of systems such as bacteriophage (phage)-based biosensors, leveraging the innate specificity and efficiency of phages to rapidly identify pathogens. However, the current genome assembly and editing methods, including Gibson Assembly, Golden Gate Assembly, and CRISPR-Cas systems, have limitations that can hinder speed and flexibility, especially when complex modifications are needed. This study introduces a novel means for generating engineered bacteriophages through a one-pot, modular in vitro genome assembly platform utilizing uracil-DNA glycosylase, which allows genome modification without requiring extended overlaps, the removal of restriction enzyme sites, a Cas system, or homologous recombination. The design also minimizes the risk of secondary structure formation (e.g., hairpins), allowing for a more efficient assembly of fragments. To demonstrate functional genome engineering, we incorporated a NanoLuc luciferase reporter gene into the T7 genome, producing a recombinant phage capable of detecting E. coli, a strategy consistent with our previous work on waterborne pathogen detection. This platform enables rapid and flexible synthetic genome construction with high functional assembly efficiency, with broad applications in phage engineering, biosensing, and synthetic biology.
The advent of the first disease-modifying therapies for Alzheimer's disease (AD) has renewed optimism for effective prevention and treatment strategies. Growing mechanistic insights indicate that AD pathogenesis is multifactorial and non-linear, better conceptualized as a circular vortex in which interconnected pathological processes reinforce one another. This complexity highlights the necessity for multiple druggable targets and combination-based therapeutic approaches. A hallmark of AD is reduced cerebral glucose utilization, revealed by positron emission tomography studies, reflecting profound metabolic disruption and mitochondrial dysfunction. Among mitochondrial candidates, 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), encoded by HSD17B10, has emerged as a protein of interest. Despite debate surrounding its substrate specificity due to conflicting in vitro data, its elevated expression in neurons and astrocytes within AD brains underscores its potential relevance. This review outlines chemical entities targeting both catalytic and non-catalytic functions of 17β-HSD10 and examines whether its inhibition offers biological efficacy and clarifies its metabolic roles in the living brain.
γ-Secretase is an intricate intramembrane aspartyl protease that cleaves within the transmembrane domain of ∼150 substrates and is considered the 'proteasome of the membrane'. This enzyme consists of four different subunits, with presenilin being the catalytic subunit. This review provides a brief overview of γ-secretase as a proteolytic enzyme, from its biochemistry and biology to its roles in disease and potential as a therapeutic target. A detailed discussion on the discovery and structure of γ-secretase is followed by a survey of its substrates, including the most studied amyloid precursor protein and the Notch1 receptor, and a description of substrate processing and sequence specificity. The role of γ-secretase in human biology and pathology is also detailed, with a particular focus on Alzheimer's disease (AD), in which the pathogenicity of the γ-secretase product amyloid-β peptide is still a matter of controversy. Lastly, the potential of γ-secretase inhibitors and modulators for the treatment of AD and other diseases is considered.
Mass spectrometry (MS)-based protein analysis is an indispensable tool in modern biomedical research. A key step in sample preparation is proteolytic digestion using enzymes with well-defined amino acid specificity, such as trypsin, chymotrypsin, and StaphV8 protease, which cleave at basic, aromatic, and acidic residues, respectively. The absence of cysteine (Cys)-specific cleavage methods is a gap in the current protein analysis toolbox. Herein, we report a chemical reagent (1) that selectively cleaves the N-terminal amide bond of Cys residues in proteins. Using glutathione as a model peptide, we investigated the reaction kinetics in detail and identified optimized conditions for protein cleavage. Using thioesterase as a model protein, we further demonstrated that 1 is fully compatible with modern MS-based proteomics workflows, including in-gel digestion, where it can be used in combination with existing proteases. This reaction proceeds rapidly and selectively in aqueous buffers, affording high yields while converting the reactive Cys side-chain thiol into a chemically inert five-membered heterocyclic moiety. This transformation eliminates the need for the commonly employed iodoacetamide capping step and introduces a distinct mass tag that facilitates downstream data analysis. Overall, these features establish 1 as a robust and practical new tool for protein analysis.
Near-infrared photoimmunotherapy (NIR-PIT) is an innovative cancer treatment modality that was approved in Japan in 2020 for the treatment of unresectable locally advanced or locally recurrent head and neck cancer. This therapy uses an antibody-dye conjugate (Ab-IR700), which consists of a monoclonal antibody targeting a specific cell-surface antigen and a phthalocyanine-based near-infrared dye, IR700, that functions as a photosensitizer. After selective accumulation in tumor tissue, Ab-IR700 is irradiated with 690 nm NIR light, which initiates a photochemical reaction that selectively damages the cell membrane of target cells, thereby inducing immunogenic cell death. Its high tumor selectivity and therapeutic efficacy establish NIR-PIT as a promising next-generation cancer therapy. However, its further application to deep-seated solid tumors remains challenging, and will require IR700 analogs and novel dye scaffolds that can be activated by longer-wavelength light to achieve greater tissue penetration and that offer greater photochemical activation efficiency. This review covers the activation mechanism of IR700, the mechanisms of cytotoxicity of NIR-PIT, emerging applications of NIR-PIT in oncology and infectious diseases, the range of dye delivery vehicles, and the development of new dyes for NIR-PIT.
As possible dual VEGFR-2/EGFR inhibitors, a new set of quinazoline-chalcone hybrid compounds (8a-h and 11a-h) was logically developed and synthesized. The synthesized compounds' chemical structures were verified by high-resolution mass spectrometry and 1H and 13C NMR. When all compounds were first tested against the MCF-7 and HepG-2 cancer cell lines at a single concentration (10 μM), several variants showed encouraging growth-inhibitory efficacy. The MTT assay was used to further assess the cytotoxic activity (IC50 values) of the most active candidates (8c, 8h, 11b, 11d, and 11f). Interestingly, the investigated compounds showed poor cytotoxicity against normal WI-38 cells and specific cytotoxicity against cancer cells. The chosen compounds demonstrated greater affinity for VEGFR-2 and efficiently inhibited both EGFR and VEGFR-2 kinases at nanomolar concentrations, as determined by enzyme inhibition studies. When compared to erlotinib (IC50 = 99.5 nM against EGFR) and sorafenib (IC50 = 30.7 nM against VEGFR-2), compound 8h exhibited the strongest dual inhibitory activity, with IC50 values of 97.7 nM against EGFR and 27.8 nM against VEGFR-2, respectively. Molecular docking and molecular dynamics simulations were used to clarify the molecular basis of their activity, and the results confirmed stable binding interactions within both kinases' ATP-binding sites. Additionally, in silico ADME and toxicity tests demonstrated good drug-likeness, pharmacokinetic characteristics, and a satisfactory safety profile. Overall, these results show that quinazoline-chalcone hybrids are effective dual EGFR/VEGFR-2 inhibitors with strong anti-cancer potential.
Acyl carrier proteins (ACPs) are dynamic, structurally conserved α-helical proteins central to many primary and secondary metabolic processes. Whilst prior engineering efforts have focused on strategic mutagenesis and "helix swaps", much of the ACP sequence design space remains underexplored. Here, we create diverse variants of the archetypal ACP subclass - AcpP - using a bespoke sequence-generating algorithm (ALGO-CP), which utilises a combined evolutionary and physicochemical design approach. Using ALGO-CP, we generated two soluble candidates - ALGO-055 and ALGO-059 - that can undergo full post-translational modification from apo → holo → acyl forms in vitro, using recombinant modifying enzymes. Building on these successful designs, we further adapted ALGO-CP to produce several chimeras, two of which - chALGO-012 and chALGO-024 - also exhibit full modifiability. We explore the structural plasticity of our ALGO variants via robust molecular dynamic simulations, and we further reveal by circular dichroism spectroscopy that ALGO-055 and ALGO-059 lack the canonical α-helical fold of an ACP, whilst remaining soluble and readily modifiable. Upon acylation of ALGO-055 and ALGO-059, we observe a marked increase in helicity indicative of protein restructuring. Of note, both ALGO-055 and ALGO-059 harbour several rare amino acid variations across their sequences, whilst preserving many important acidic "hotspots" involved in key protein-protein interactions. By testing the limits of the AcpP design space, our findings suggest that some key aspects of ACP behaviour (specifically post-translational modification) can be retained independently of the canonical structure. This work establishes a foundation for probing ACP sequence diversity through a hybrid computational-experimental approach. ALGO-CP is available under AGPL3.0 license: https://github.com/MAHerrera-94/ALGO_CP.
Crataegus monogyna is widely used in traditional medicine due to its rich content of bioactive compounds. The present study aimed to evaluate the influence of extraction parameters, including solvent concentration, extraction time, temperature, and solid-to-liquid ratio, on total phenolics, total flavonoids, antioxidant DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), FRAP (ferric reducing antioxidant power), and CUPRAC (cupric reducing antioxidant capacity)), and enzyme inhibitory properties (α-amylase and tyrosinase). Furthermore, an Artificial Neural Network (ANN) model was applied to optimize the extraction conditions. The results demonstrated that extraction conditions significantly affect both chemical composition and biological activity. The optimal conditions (70% ethanol, 30 min, 45 °C, (1 : 30)) yielded extracts with high total phenolic (109.15 mg GAE per g), and total flavonoid content (70.74 mg RE per g), strong antioxidant activity (DPPH: 473.57 mg TE per g, ABTS: 537.58 mg TE per g, CUPRAC: 407.11 mg TE per g, FRAP: 393.91 mg TE per g) and notable enzyme inhibitory potential (0.53 mmol ACAE per g against α-amylase and 75.00 mg KAE per g against tyrosinase). The ANN model showed excellent predictive performance, confirming its suitability for modeling and optimization of complex extraction systems. The present study provides comprehensive insights into optimized ultrasound-assisted extraction methods for the recovery of maximum bioactive compounds and biological activities (antioxidant and enzyme inhibition effect) from C. monogyna flowering branches using experimental design and ANN model. These findings provide a reliable basis for the development of functional and pharmaceutical products.