Advances In Chemical Modification Research Articles

Molecularly Modified Electrodes for Efficient Triboelectric Nanogenerators

The integration of organic molecules into monolayers on triboelectric layers and electrodes has significantly improved the performance of triboelectric nanogenerators (TENGs) in recent years. By modifying surfaces at the molecular level, one can enhance durability, power density, and cost‐efficiency, leading to flexible, lightweight, and more efficient devices. A simple chemistry of organic monolayer formation allows a precise control over orientation, coverage, consistency, and functionality. These monolayers boost surface charge density and output voltage while influencing surface polarization and dipole interactions. This review focuses on recent advances in chemical modification of electrodes for controlling surface charge density and altering surface dipoles, emphasizing the significance of organic monolayers. A new concept of Schottky‐based TENGs is also introduced that explores chemically modified sliding surfaces. Furthermore, the importance of flexoelectricity and its contribution to triboelectricity is discussed. By addressing current challenges and outlining future directions, this review underscores the crucial role of surface chemistry in advancing TENGs.

Screening Splice-Switching Antisense Oligonucleotides in Pancreas-Cancer Organoids.

Aberrant alternative splicing is emerging as a cancer hallmark and a potential therapeutic target. It is the result of dysregulated or mutated splicing factors, or genetic alterations in splicing-regulatory cis-elements. Targeting individual altered splicing events associated with cancer-cell dependencies is a potential therapeutic strategy, but several technical limitations need to be addressed. Patient-derived organoids are a promising platform to recapitulate key aspects of disease states, and to facilitate drug development for precision medicine. Here, we report an efficient antisense-oligonucleotide (ASO) lipofection method to systematically evaluate and screen individual splicing events as therapeutic targets in pancreatic ductal adenocarcinoma organoids. This optimized delivery method allows fast and efficient screening of ASOs, e.g., those that reverse oncogenic alternative splicing. In combination with advances in chemical modifications of oligonucleotides and ASO-delivery strategies, this method has the potential to accelerate the discovery of antitumor ASO drugs that target pathological alternative splicing.

Nucleic acid-based therapeutics for the treatment of central nervous system disorders.

Nucleic acid-based therapeutics (NBTs) are an emerging class of drugs with potential for the treatment of a wide range of central nervous system conditions. To date, pertaining to CNS indications, there are two commercially available NBTs and a large number of ongoing clinical trials. However, these NBTs are applied directly to the brain due to very low blood brain barrier permeability. In this review, we outline recent advances in chemical modifications of NBTs and NBT delivery techniques intended to promote brain exposure, efficacy, and possible future systemic application.

Drug Metabolism and Pharmacokinetics of Antisense Oligonucleotide Therapeutics: Typical Profiles, Evaluation Approaches, and Points to Consider Compared with Small Molecule Drugs.

Oligonucleotide therapeutics are attracting attention as a new treatment modality for a range of diseases that have been difficult to target using conventional approaches. Technical advances in chemical modification and drug delivery systems have led to the generation of compounds with excellent profiles as pharmaceuticals, and 16 oligonucleotide therapeutics have been marketed to date. There is a growing need to develop optimal and efficient approaches to evaluate drug metabolism and pharmacokinetics (DMPK) and drug-drug interactions (DDIs) of oligonucleotide therapeutics. The DMPK/DDI profiles of small molecule drugs are highly diverse depending on their structural and physicochemical characteristics, whereas oligonucleotide therapeutics share similar DMPK profiles within each chemistry type. Most importantly, the mechanisms and molecules involved in the distribution and metabolism of oligonucleotides differ from those of small molecules. In addition, there are considerations regarding experimental approaches in the evaluation of oligonucleotides, such as bioanalytical challenges, the use of radiolabeled tracers, materials for in vitro metabolism/DDI studies, and methods to study biodistribution. In this review, we attempt to summarize the DMPK characteristics of antisense oligonucleotide (ASO) therapeutics and discuss some of the issues regarding how to optimize the evaluation and prediction of the DMPK and DDI of ASOs.

Recent developments in lignin modification and its application in lignin‐based green composites: A review

AbstractLignins are the most important aromatic renewable natural resource today, serving as a sustainable, environmentally acceptable alternative feedstock to fossil‐derived chemicals and polymers in a vast scope of value‐added applications. Lignin is a biopolymeric molecule that, together with cellulose, is a fundamental component of higher vascular plants structural cell walls. It can be extracted from by‐products of the pulp and paper industries, agricultural waste and residues, and biorefinery products. Lignin properties may vary depending on source and extraction method with carbon and aromatic as the main compositions in lignin structure. These rich compositions make lignin more valuable, allowing for the creation of high‐value‐added green composites. However, the complex structure of lignin creates low reactivity to interact with crosslinker, and hence chemical modification is substantial to overcome this problem. This review aimed to present and discuss lignin structure, variation of lignin chemical properties regarding its source and extraction process, recent advances in chemical modification of lignin to enhance its reactivity, and potential applications of modified lignin for manufacturing value‐added biocomposites with enhanced properties and lower environmental impact, such as food handling/packaging, seed coating, automotive devices, 3D printing, rubber industry, and wood adhesives.

Research Progress on Chemical Modification and Application of Cellulose: A Review

Cellulose is a rich natural polymer material, which has the characteristics of biodegradability, environmental friendliness and good biocompatibility. However, compared with conventional materials, there are some shortcomings in performance, such as intolerance corrosion, limited strength and so on. The chemical modification of cellulose not only retains its own excellent characteristics, but also introduces functional groups to endow it with specific properties. The chemical modification and utilization of cellulose has been the focus of research. In this paper, the latest advances in chemical modification of cellulose, such as esterification, etherification and grafting modification, are introduced. The research and application results of cellulose derivatives in food, wastewater treatment, medicine and papermaking in recent years are reviewed.

Recent Advances in Chemical Modifications of Nitriles

AbstractNitrile represents a synthetically important class of compounds, relevant to the preparation of fine organic chemicals, natural products, and biologically active molecules. The electronegative nitrogen atom and electropositive carbon atom of cyano group endow nitriles with rich and diverse chemical properties. Traditional chemical transformations of nitriles usually involve the use of strong acids, bases, and other harsh conditions. To overcome these limitations, various catalytic methods have been explored both in homogeneous and heterogeneous systems. In this review, we summarize some of the recent progress on the development of efficient synthetic methods involving nitriles. Especially, the classic transformations of nitriles including hydration, hydrolysis and reduction reactions are discussed in detail, which provide rapid access to a series of important small molecules, such as amides, ketones, amines, and imines. The reaction development, as well as the design of the catalytic system will be discussed with special emphasis placed on the mechanistic aspects.

Capturing the RNA castle: Exploiting MicroRNA inhibition for wound healing.

The growing pipelines of RNA-based therapies herald new opportunities to deliver better patient outcomes for complex disorders such as chronic nonhealing wounds associated with diabetes. Members of the microRNA (miRNA) family of small noncoding RNAs have emerged as targets for diverse elements of cutaneous wound repair, and both miRNA enhancement with mimics or inhibition with antisense oligonucleotides represent tractable approaches for miRNA-directed wound healing. In this review, we focus on miRNA inhibition strategies to stimulate skin repair given advances in chemical modifications to enhance the performance of antisense miRNA (anti-miRs). We first explore miRNAs whose inhibition in keratinocytes promotes keratinocyte migration, an essential part of re-epithelialisation during wound repair. We then focus on miRNAs that can be targeted for inhibition in endothelial cells to promote neovascularisation for wound healing in the context of diabetic mouse models. The picture that emerges is that direct comparisons of different anti-miRNAs modifications are required to establish the most translationally viable options in the chronic wound environment, that direct comparisons of the impact of inhibition of different miRNAs are needed to quantify and rank their relative efficacies in promoting wound repair, and that a standardised human ex vivo model of the diabetic wound is needed to reduce reliance on mouse models that do not necessarily enhance mechanistic understanding of miRNA-targeted wound healing.

Synthetic blood and blood products for combat casualty care and beyond.

Synthetic biology adopts an engineering design approach to create innovative treatments that are reliable, scalable, and customizable to individual patients. Interest in substitutes for allogenic blood components, primarily red blood cells and platelets, increased in the 1980s because of concerns over infectious disease transmission. However, only now, with emerging synthetic approaches, are such substitutes showing genuine promise. Affordable alternatives to donated blood would be of enormous benefit worldwide. Several approaches to replacing the oxygen-carrying function of red cells are under advanced investigation. Hemoglobin-based oxygen carriers incorporate modifications to reduce the renal toxicity and nitric oxide scavenging of free hemoglobin. While use of earlier-generation hemoglobin-based oxygen carriers may be limited to circumstances in which blood transfusion is not an option, recent advances in chemical modification of hemoglobin may eventually overcome such problems. Another approach encases hemoglobin molecules in biocompatible synthetic nanoparticles. An alternative is the ex vivo production of red cells in bioreactors, with or without genetic manipulation, that offers the potential of a universal donor product. Various strategies to manufacture synthetic platelets are also underway, ranging from simple phospholipid liposomes encapsulating adenosine diphosphate and decorated with fibrinogen fragments, to more complex capsules with multiple receptor peptide sequences. Ex vivo production of platelets in bioreactors is also possible including, for example, platelets derived from induced pluripotent stem cells that are differentiated into a megakaryocytic lineage. Prior to clinical use, trials assessing synthetic blood components must evaluate meaningful safety and effectiveness outcomes in relatively large numbers of critically ill patients. Overcoming these challenges may be as much a hurdle as product design. This article reviews the state of the science of the synthetic biology approach to developing blood component substitutes.

Recent advances in chemical modifications of guide RNA, mRNA and donor template for CRISPR-mediated genome editing.

The discovery and applications of clustered regularly interspaced short palindromic repeat (CRISPR) systems have revolutionized our ability to track and manipulate specific nucleic acid sequences in many cell types of various organisms. The robustness and simplicity of these platforms have rapidly extended their applications from basic research to the development of therapeutics. However, many hurdles remain on the path to translation of the CRISPR systems to therapeutic applications: efficient delivery, detectable off-target effects, potential immunogenicity, and others. Chemical modifications provide a variety of protection options for guide RNA, Cas9 mRNA and donor templates. For example, chemically modified gRNA demonstrated enhanced on-target editing efficiency, minimized immune response and decreased off-target genome editing. In this review, we summarize the use of chemically modified nucleotides for CRISPR-mediated genome editing and emphasize open questions that remain to be addressed in clinical applications.

Advances in chemical modifications of starches and their applications

Starch is a homopolysaccharide made up of glucose units which are linked together via a glycosidic linkage. This biopolymer is well known for its low cost, biodegradability, renewability and easy availability. In spite of all these beauties, starch has some problems with their solubility in water, retrogradation, loss of viscosity due to rupturing of glucosidic bond when subjected to treatment and absence of some groups of primary importance like different functional groups especially carboxylic group, ester group, ether group and amino group. In order to overcome these shortcomings and enhance its applications, starch must be modified. The modification can be done chemically, physically and enzymatically, but noteworthy one is the chemical modification. In this review article, we focused on the recently used ways of chemical modification such as acid hydrolysis, cross-linking, acetylation/esterification, dual modification, oxidation and grafting of starch, and their properties. This review article highlighted the application of modified starch as an adsorbent for the removal of ammonia, phenol, heavy metals, and dyes.

Aligned Nanofibrillar Scaffolds for Controlled Delivery of Modified mRNA.

RNA-based vector delivery is a promising gene therapy approach. Recent advances in chemical modification of mRNA structure to form modified mRNA (mmRNA or cmRNA or modRNA) have substantially improved their stability and translational efficiency within cells. However, mmRNA conventionally delivered in solution can be taken up nonspecifically or become cleared away prematurely, which markedly limits the potential benefit of mmRNA therapy. To address this limitation, we developed mmRNA-incorporated nanofibrillar scaffolds that could target spatially localized delivery and temporally controlled release of the mmRNA both in vitro and in vivo. To establish the efficacy of mmRNA therapy, mmRNA encoding reporter proteins such as green fluorescence protein or firefly luciferase (Fluc) was loaded into aligned nanofibrillar collagen scaffolds. The mmRNA was released from mmRNA-loaded scaffolds in a transient and temporally controlled manner and induced transfection of human fibroblasts in a dose-dependent manner. In vitro transfection was further verified using mmRNA encoding the angiogenic growth factor, hepatocyte growth factor (HGF). Finally, scaffold-based delivery of HGF mmRNA to the site of surgically induced muscle injury in mice resulted in significantly higher vascular regeneration after 14 days, compared to implantation of Fluc mmRNA-releasing scaffolds. After transfection with Fluc mmRNA-releasing scaffold in vivo, Fluc activity was detectable and localized to the muscle region, based on noninvasive bioluminescence imaging. Scaffold-based local mmRNA delivery as an off-the-shelf form of gene therapy has broad translatability for treating a wide range of diseases or injuries.

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy.

An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

Recent advances in chemical modifications of graphene

Graphene has attracted the interest of chemists, physicists, and materials scientists due to its extraordinary structural, mechanical, and electronic properties. While pristine graphene is desirable for applications that require a high electrical conductivity, many other applications require modified or functionalized forms of graphene, such as graphene oxide, reduced graphene, or other functionalized forms. Structurally modifying graphene through chemical functionalization reveals the numerous possibilities for tuning its structure; several chemical and physical functionalization methods have been explored to improve the stabilization and modification of graphene. In this review, we report recent progress towards the chemical modification of graphene, including both covalent and noncovalent methods, for use in various applications.

MS-Monitored Conjugation of Poly(ethylene glycol) Monomethacrylate to RGD Peptides.

Development of biologically active polymers is an active area of research due to their applications in varied and diverse fields of biomedical research: cell adhesion, tissue proliferation, and drug delivery. Recent advances in chemical modification allow fine-tuning of the properties of biomedical polymers to improve their applications: blood circulation half-life, stimuli-responsive degradation, site-specific targeting, drug loading, etc. In this article, convergent synthesis of polymerizable macromonomers bearing a site-specific ligand (RGD peptide) using a low molecular weight MA-poly(ethylene glycols) (PEGs) is presented. The method affords macromonomers useful as the starting materials to produce biomedical polymers. We found matrix assisted laser desorption/ionization mass spectromerty convenient in monitoring the conjugation process via step-by-step following of PEG modification.

Artificially Created Nucleic Acids and Peptides/Proteins in Chemical Biology

Nucleic acids—DNA and RNA—have been chosen by Mother Nature as the key players for orchestrating the preservation, transfer, and expression of genetic information in all the biological systems on Earth. RNA has also been enlisted to carry out other important cellular functions, such as catalysis and molecular recognition. Within the hands of scientists, the function of nucleic acids has been significantly expanded beyond what is known in nature, and as a result, we are now in the possession of a large array of synthetic, nucleic acid-based catalysts (ribozymes and DNAzymes) and receptors (DNA and RNA aptamers). DNA as a genetic material itself has also been subjected to various chemical modifications in efforts to derive significantly altered or even completely new genetic systems. These systems can be used to create novel peptides and proteins that offer enhanced activities or even completely new properties over their natural protein counterparts. Furthermore, many artificially engineered nucleic acids and proteins have found useful applications as biosensors, diagnostic agents, and therapeutic drugs. This special issue is assembled to reflect recent progress in the important research arena of artificially engineered nucleic acids and proteins. This issue comprises 10 reviews and 7 research articles that can be grouped into three sections. The first section deals mainly with research on xeno-nucleic acids (XNAs)—nonnatural nucleic acid analogs with significantly altered sugar and/or phosphate backbones. D.-A. Catana et al. provide a review on the use of dinucleotides of dioxaphosphorinane-constrained nucleic acids (CNAs) to tune nucleic acid structures. This is followed by a review by E. Rozners on recent advances in chemical modifications of peptide nucleic acids (PNAs). G. Upert et al. then present a research article on designing cyclic and hairpin PNAs as inhibitors for HIV replication. Z. Wang et al. also present a research article where PNA probes were utilized for live cell imaging of mRNA expression. In their research article, T. Yamamoto et al. examine the gene-silencing effect of bridged/locked nucleic acids (BNA/LNAs). This section is closed out with a research article by S. Saxena et al. in which the molecular crowding effect on the structure and function of RecG (a helicase) was examined. The second section includes four reviews and three research articles discussing the creation of novel peptides, proteins, transfer RNAs, and peptide mimicries using various selection or screening methods. K. Fukunaga and M. Taki provide a review on the phage display technique with a particular focus on tips for conducting successful phage display experiments. Within the same topic, T. Matsubara reviews the use of phage display for the creation of carbohydrate-mimetic peptides. These are followed by a research article by T. Sumida et al. exploiting the mRNA display technique for the selection of anti-p53 Fab fragments. There are two papers concerning the in vitro compartmentalization (IVC) technique, which offers an excellent way to link a genotype to a phenotype in a physically confined environment: the first is a review article by T. Nishikawa et al. on evolving proteins using IVC and the second is a research article by A. Ogawa et al. where IVC was used to select functional transfer RNAs. T. Kawakami and H. Murakami discuss, in their review article, potential applications of a translation system with a reprogrammed genetic code to prepare a peptide mimetic library. Finally, J. K. Pokorski and D. H. Appella present an on-bead screening approach to create peptide mimicries. The last section of the issue consists of four review papers on the selection and application of functional nucleic acids. M. McKeague and M. C. DeRosa survey DNA and RNA aptamers derived by SELEX (systematic evolution of ligands via exponential enrichment) for small molecule binding, along with the compilation of nearly 40 improved methodologies of SELEX. K. Tram et al. review the application of fluorescently dressed RNA-cleaving DNAzymes for biosensing. Y. M. Chang et al. discuss the cell-SELEX technique for biomarker discovery. In addition, Y. Kasahara and M. Kuwahara provide a review on SELEX experiments exploring chemically modified nucleic acid libraries. The ultimate goal in this research arena is to generate scientific knowledge and produce new technologies that will enable the engineering of novel or improved molecular systems to control biological activities at will. Along the way, researchers may help shine light on one of the biggest mysteries surrounding the origin and evolution of life on Earth—the question of why Mother Nature has selected 4 nucleotides to construct nucleic acids and 20 amino acids to construct proteins. We hope this special issue can further spur research efforts in this area.

Recent Advances in Chemical Modification of Peptide Nucleic Acids

Peptide nucleic acid (PNA) has become an extremely powerful tool in chemistry and biology. Although PNA recognizes single-stranded nucleic acids with exceptionally high affinity and sequence selectivity, there is considerable ongoing effort to further improve properties of PNA for both fundamental science and practical applications. The present paper discusses selected recent studies that improve on cellular uptake and binding of PNA to double-stranded DNA and RNA. The focus is on chemical modifications of PNA's backbone and heterocyclic nucleobases. The paper selects representative recent studies and does not attempt to provide comprehensive coverage of the broad and vibrant field of PNA modification.

Applications of nucleic acid technology in the CNS.

This review examines applications of nucleic acid technology in the form of catalytic nucleic acids (ribozymes and DNAzymes) and RNA interference (RNAi) in the CNS. The basic mechanism of catalytic nucleic acids and RNAi is reviewed, and potentials and problems highlighted. Recent advances in chemical modifications and delivery techniques are summarized. Applications in the CNS, including their use in primary neuronal cells, organotypic slice culture and the brain in vivo are further discussed.