Search Results (504)

Background/Objectives: The potential of DNA as an information-dense storage medium has inspired a broad spectrum of creative systems. In particular, hybrid biomolecular systems that integrate new materials and chemistries with DNA could drive novel functions. In this work, we explore the potential for proteins to serve as molecular file addresses. We stored DNA-encoded data in yeast and leveraged yeast surface display to readily produce the protein addresses and make them easy to access on the cell surface. Methods: We generated yeast populations that each displayed a distinct protein on their cell surfaces. These proteins included binding partners for cognate antibodies as well as chromatin-associated proteins that bind post-translationally modified histone peptides. For each specific yeast population, we transformed a library of hundreds of DNA sequences collectively encoding a specific image file. Results: We first demonstrated that the yeast retained file-encoded DNA through multiple cell divisions without a noticeable skew in their distribution or a loss in file integrity. Second, we showed that the physical act of sorting yeast displaying a specific file address was able to recover the desired data without a loss in file fidelity. Finally, we showed that analog addresses can be achieved by using addresses that have overlapping binding specificities for target peptides. Conclusions: These results motivate further exploration into the advantages proteins may confer in molecular information storage. Full article

The virus-first theory presents a model in which viral lineages emerged before cells. This proposal aims to give the theory greater relevance by offering a plausible evolutionary framework that explains both (i) the origin of viruses from prebiotic chemistry and (ii) how viruses contributed to the emergence of cells. Here, we propose that viruses should be understood as a distinct class of ribonucleoprotein (RNP) systems, some of which evolved directly from the RNP-world. In our model, simple progenotes produced capsid-like particles through the evolution of a single gene encoding a self-assembling peptide. This allowed the formation of icosahedral shells around RNA genomes, as observed today in certain viral families whose capsids consist of ~60 identical subunits derived from a single gene product. These early capsids enabled mobility and protection, representing key intermediates toward biological complexity. Over time, some of those populations acquired additional peptides and evolved more elaborate architectures. Finally, the incorporation of lipid-binding domains in those capsid-like peptides allowed the formation of proteolipidic membranes akin to those found in modern cells. This model provides a gradualistic and logically coherent evolutionary path from the RNP-world to the emergence of cellular life, emphasizing the foundational role of viruses in early evolution. Full article

Delivering of hydrophobic drugs by polymeric nanoparticles is an intensively investigated research and development field worldwide due to the insufficient solubility of many existing and potential new drugs in aqueous media. Among polymeric nanoparticles, micelles of biocompatible amphiphilic block copolymers are among the most promising candidates for solubilization, encapsulation, and delivery of hydrophobic drugs to improve the water solubility and thus the bioavailability of such drugs. In this study, amphiphilic ABA triblock copolymers containing biocompatible hydrophilic hyperbranched (dendritic) polyglycerol (HbPG) outer and hydrophobic poly(tetrahydrofuran) (PTHF) inner segments were synthesized using amine-telechelic PTHF as a macroinitiator for glycidol polymerization. These hyperbranched–linear–hyperbranched block copolymers form nanosized micelles with 15–20 nm diameter above the critical micelle concentration. Coagulation experiments proved high colloidal stability of the aqueous micellar solutions of these block copolymers against temperature changes. The applicability of block copolymers as drug delivery systems was investigated using curcumin, a highly hydrophobic, water-insoluble, natural anti-cancer agent. High and efficient drug solubilization up to more than 3 orders of magnitude to that of the water solubility of curcumin (>1500-fold) is achieved with the HbPG-PTHF-HbPG block copolymer nanomicelles, locating the drug in amorphous form in the inner PTHF core. Outstanding stability of and sustained curcumin release from the drug-loaded block copolymer micelles were observed. The in vitro bioactivity of the curcumin-loaded nanomicelles was investigated on U-87 glioblastoma cell line, and an optimal triblock copolymer composition was found, which showed highly effective cellular uptake and no toxicity. These findings indicate that the HbPG-PTHF-HbPG triblock copolymers are promising candidates for advanced drug solubilization and delivery systems. Full article

Peptides are substances with numerous applications in chemistry, biology, medicine, and agriculture. Systematization of knowledge related to peptides may well have not only scientific research but also economic consequences. This study examines the antioxidant activity of peptides and the ACE-inhibitory capacity of peptides. Peptides are considered here containing three or four amino acids. Nevertheless, instead of considering peptides as traditional molecules, an attempt is made here to systematize the corresponding endpoints as mathematical functions of lists of amino acids, rather than considering the corresponding atoms and covalent bonds. New techniques that may be useful in theory and in practice for the development of quantitative structure–property/activity relationships (QSPRs/QSARs) related to certain types of biological activity of peptides are proposed and discussed. Full article

In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first converted in 3,7-(prop-2-yn-yloxy)flavone (2) and acetobromo-α-D-glucose (3) was converted into 2,3,4,6-tetra-O-acetyl-β-glucopyranosyl azide (4). Subsequently, a click reaction was performed via copper-catalysed cycloaddition (CuAAC) between 2 and 4, as well as between 2 and 2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranosyl (AG931) and, 2 and commercial 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl (AG358), resulting in three distinct disubstituted flavone glycosides (5a–5c). Biological assays performed on L929 fibroblast cell lines and human glioblastoma astrocytoma U-251 cell lines indicated cytocompatibility with fibroblasts and reduced metabolic activity of GBM cells in the presence of compound 5b and 5c. To enhance therapeutic effect, improve local drug delivery, and overcome solubility issues of these high molecular weight compounds, the synthesised compounds were encapsulated in polymeric particles (polymersomes, PMs) composed of polylactic acid-polyethylene glycol (PEG-PLA) functionalized, once more by click chemistry, with 0.1 mol% transferrin mimetic (T7—HRPYIAH) peptide. The PMs were prepared by solvent displacement and exhibited stability over 100 days, encapsulation efficiency of 39–93%, and mean size diameters of 120–180 nm. The toxicity assays of the PMs on the U-251 cell line showed a significant decrease in metabolic activity, supporting the potential of this delivery system against GBM. Among the PMs tested, the flavone 5c-based PM demonstrated the highest efficacy. Full article

Radix Pseudostellariae (Tai-Zi-Shen), the dried tuberous root of the Caryophyllaceae plant Pseudostellaria heterophylla (Miq.) Pax (P. heterophylla), has been widely used in traditional Chinese medicine (TCM) for thousands of years. It is slightly bitter, neutral in nature, associated with the spleen and lung meridians, and used for nourishing qi, invigorating the spleen, as well as promoting body fluid production and moistening the lungs. In recent years, with the development in natural product chemistry, cyclic peptides, as some of the active constituents derived from P. heterophylla, have gained increasing attention. These cyclic peptides demonstrate a broad range of biological activities, including anticancer, antioxidant, and immunomodulatory effects, as well as cognitive benefits. This review provides an overview of the chemical characteristics and preparation strategies of cyclic peptides from P. heterophylla, and their biological activities and potential mechanisms are also described. The presented work establishes a scientific framework to facilitate the future research and development of P. heterophylla cyclic peptides as potential therapeutic agents. Full article

Short- and medium-sized peptides have long been used as effective and versatile organocatalysts. In the early 80s, Inoue used diketopiperazines in the Strecker reaction, while Juliá and Colonna reported the epoxidation of chalcone catalyzed by poly-L-Ala. Since then, a variety of peptide-catalyzed reactions have been described. However, peptide synthesis typically implicates the use of toxic reagents and generates wastes; therefore, peptide recycling is expected to significantly improve the overall sustainability of the process. Easy recovery and recycling of peptide catalysts can be expediently attained by covalent binding, inclusion, or adsorption. In addition, immobilization can significantly accelerate the screening of new peptide catalysts. For these reasons, diverse supports have been tested, including natural or synthetic polymers, porous polymeric networks, inorganic porous materials, organic-inorganic hybrid materials, and finally metal–organic frame-works. Full article

In non-ribosomal peptide synthesis of cyanobacteria, promiscuous adenylation domains allow the incorporation of clickable non-natural amino acids into peptide products—namely into microcystins (MCs) or into anabaenopeptins (APs): 4-azidophenylalanine (Phe-Az), N-propargyloxy-carbonyl-L-lysine (Prop-Lys), or O-propargyl-L-tyrosine (Prop-Tyr). Subsequently, chemo-selective labeling is used to visualize the clickable cyanopeptides using Alexa Fluor 488 (A488). In this study, the time-lapse build up or decline of azide- or alkyne-modified MCs or APs was visualized during maximum growth, specifically MC biosynthesis in Microcystis aeruginosa and AP biosynthesis in Planktothrix agardhii. Throughout the time-lapse build up or decline, the A488 signal occurred with heterogeneous intracellular distribution. There was a fast increase or decrease in the A488 signal for either Prop-Tyr or Prop-Lys, while a delayed or unobservable A488 signal for Phe-Az was related to increased cell size as well as a reduction in growth and autofluorescence. The proportion of clickable MC/AP in peptide extracts as recorded by a chemical–analytical technique correlated positively with A488 labeling intensity quantified via laser-scanning confocal microscopy for individual cells or via flow cytometry at the population level. It is concluded that chemical modification of MC/AP can be used to track intracellular dynamics in biosynthesis using both analytical chemistry and high-resolution imaging. Full article

Antimicrobial peptides (AMPs) have emerged as promising candidates in the fight against multidrug-resistant pathogens due to their broad-spectrum antimicrobial activity and low potential for resistance development. However, their clinical application is limited by poor stability and susceptibility to enzymatic degradation. This study aims to address these limitations by synthesizing a series of cyclic hexapeptides using the hydrazide method and evaluating their antimicrobial activity and stability. The hydrazide method facilitated the synthesis of 11 cyclic peptides through a reaction between C-terminal hydrazides and cysteine-containing peptides. Antimicrobial assays showed that Cy-f2 and Cy-f4 exhibited potent inhibitory effects against different kinds of bacteria, including E. coli, Staphylococcus aureus, and S. aureus. Hemolysis assays revealed minimal red blood cell lysis at effective antimicrobial concentrations, indicating good biocompatibility. Stability tests demonstrated improved stability of the cyclic peptides compared to linear counterparts in SGF and 80 °C. In conclusion, the cyclic hexapeptides synthesized in this study demonstrate excellent antimicrobial activity, enhanced stability, and low toxicity, suggesting their potential as new candidates for treating drug-resistant bacterial infections. Full article

Heterocycle cores are widely used in medicinal chemistry for developing bioactive compounds. In this scenario, using cheap and accessible starting material to build these heterocycles is desirable to obtain new drug candidates for cost-efficient processes. One easily accessible source of starting material are amino acids. Usually, these compounds are employed in peptide synthesis, but their use for building heterocycle frameworks presents another appealing opportunity. Therefore, this review highlights the application of histidine and tryptophan, two heteroaromatic amino acids, in fused heterocyclic scaffold synthesis and their use in bioactive compounds. Full article

Drug conjugates, in which chemotherapeutic or cytotoxic agents are coupled to targeting or delivering macromolecules like peptides or proteins via a linker, revolutionize cancer treatment. While protein-drug and antibody-drug conjugates have already secured a role in clinical oncology, peptide–drug conjugates (PDCs) are emerging as a promising alternative, offering enhanced efficacy and fewer side effects compared to the free drug molecules. Comprehensive chemical and biological investigation of PDCs is crucial during drug development and optimization, paving the way for the next generation of targeted therapies. Anthracycline-containing peptide conjugates have emerged as promising candidates in targeted cancer therapies due to their ability to deliver cytotoxic agents directly to tumor cells. However, their structural complexity poses significant analytical challenges, particularly in mass spectrometric characterization. Accurate identification and quantification of these conjugates are critical for assessing their stability, efficacy, and mechanism of action. This article explores the major difficulties encountered during mass spectrometry (MS) analysis of anthracycline-peptide conjugates, focusing on ionization issues, fragmentation behavior, and challenges of detection from biological matrix. Full article

Surface display technology has revolutionized whole-cell biocatalysis by enabling efficient enzyme immobilization on microbial cell surfaces. Compared with traditional enzyme immobilization, this technology has the advantages of high enzyme activity, mild process, simple operation and low cost, which thus has been widely studied and applied in various fields. This review explores the principles, optimization strategies, applications in the food industry, and future prospects. We summarize the membrane and anchor protein structures of common host cells (Escherichia coli, Bacillus subtilis, and yeast) and discuss cutting-edge optimization approaches, including host strain genetic engineering, rational design of anchor proteins, innovative linker peptide engineering, and precise regulation of signal peptides and promoters, to maximize surface display efficiency. Additionally, we also explore its diverse applications in food processing and manufacturing, additive synthesis, food safety, and other food-related industries (such as animal feed and PET packaging degradation), demonstrating their potential to address key challenges in the food industry. This work bridges fundamental research and industrial applications, offering valuable insights for advancing agricultural and food chemistry. Full article

Neurological disorders, encompassing neurodegenerative and neuroinflammatory conditions, present significant public health and clinical challenges. Recent research has elucidated the pivotal role of various enzymes in the onset and progression of these disorders. This review explores the therapeutic potential of targeting these enzymes with natural and synthetic molecules. Key enzymes, including acetylcholinesterase, monoamine oxidase, beta-secretase, tau kinases, caspases, and cyclooxygenase-2, are implicated in diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Modulating these enzymes can alleviate symptoms, slow disease progression, or reverse pathological changes. Natural molecules derived from plants, microbes, seaweeds, and animals have long been noted for their therapeutic potential. Their ability to interact with specific enzymes with high specificity and minimal side effects makes them promising candidates for treatment. These natural agents provide a foundation for developing targeted therapies with improved safety profiles. Simultaneously, the development of synthetic chemistry has resulted in molecules designed to inhibit neurodegenerative enzymes with precision. This review examines the progress in creating small molecules, peptides, and enzyme inhibitors through sophisticated drug design techniques. It evaluates the efficacy, safety, and mechanisms of these synthetic agents, highlighting their potential for clinical application. The review offers a comprehensive overview of recent advancements in enzyme-targeted therapies for neurological disorders, covering both natural and synthetic molecules investigated in preclinical and clinical settings. It discusses the mechanisms through which these molecules exert their effects, the challenges faced in their development, and future research directions. By synthesizing current knowledge, this paper aims to illuminate the potential of enzyme-targeted interventions in managing neurological disorders, showcasing both the promise and limitations of these approaches. Full article

Kapakahines A–G are natural products isolated from the marine sponge Carteriospongia sp., characterized by complex molecular architectures composed of fused rings and diverse functional groups. Preliminary studies have indicated that some of these peptides may exhibit cytotoxic and antitumor activities, which has prompted interest in further exploring their chemical and pharmacokinetic properties. Computational chemistry—particularly Conceptual Density Functional Theory (CDFT)-based Computational Peptidology (CP)—offers a valuable framework for investigating such compounds. In this study, the CDFT-CP approach is applied to analyze the structural and electronic properties of Kapakahines A–G. Alongside the calculation of global and local reactivity descriptors, predicted ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles and pharmacokinetic parameters, including pKa and LogP, are evaluated. The integrated computational analysis provides insights into the stability, reactivity, and potential drug-like behavior of these marine-derived cyclopeptides and contributes to the theoretical groundwork for future studies aimed at optimizing their bioactivity and safety profiles. Full article

DNA information storage holds tremendous potential due to its scalability, long lifespan, and environmental sustainability. The synthesis and reading of complex DNA data structures are of central importance. In this work, we propose new encoding schemes through novel synthesis methods of DNA and peptide nanostructures. Silicon nitride (SiN_x) solid-state nanopores (ssNPs) are employed as the detection platform to enable scalable and inexpensive reading. This approach is no longer constrained by the limitations of single-base sequencing technologies. Peptide nanostructures are introduced as a data medium via click-chemistry, expanding encoding sources. By integrating a photosensitive PC-linker, this approach endows the data chain with functionalities for encryption and data formatting, enhancing the security and organization of biological information storage. Our study presents a comprehensive framework for data management from data synthesis to post-processing, which includes encryption, decryption, and erasure functionalities. Full article