Chemical Modification Approaches Research Articles

Bioengineering of air-filled protein nanoparticles by genetic and chemical functionalization

BackgroundVarious bacteria and archaea, including halophilic archaeon Halobacterium sp. NRC-1 produce gas vesicle nanoparticles (GVNPs), a unique class of stable, air-filled intracellular proteinaceous nanostructures. GVNPs are an attractive tool for biotechnological applications due to their readily production, purification, and unique physical properties. GVNPs are spindle- or cylinder-shaped, typically with a length of 100 nm to 1.5 μm and a width of 30–250 nm. Multiple monomeric subunits of GvpA and GvpC proteins form the GVNP shell, and several additional proteins are required as minor structural or assembly proteins. The haloarchaeal genetic system has been successfully used to produce and bioengineer GVNPs by fusing several foreign proteins with GvpC and has shown various applications, such as biocatalysis, diagnostics, bioimaging, drug delivery, and vaccine development.ResultsWe demonstrated that native GvpC can be removed in a low salt buffer during the GVNP purification, leaving the GvpA-based GVNP's shell intact and stable under physiological conditions. Here, we report a genetic engineering and chemical modification approach for functionalizing the major GVNP protein, GvpA. This novel approach is based on combinatorial cysteine mutagenesis within GvpA and genetic expansion of the N-terminal and C-terminal regions. Consequently, we generated GvpA single, double, and triple cysteine variant libraries and investigated the impact of mutations on the structure and physical shape of the GVNPs formed. We used a thiol–maleimide chemistry strategy to introduce the biotechnological relevant activity by maleimide-activated streptavidin–biotin and maleimide-activated SpyTag003-SpyCatcher003 mediated functionalization of GVNPs.ConclusionThe merger of these genetic and chemical functionalization approaches significantly extends these novel protein nanomaterials' bioengineering and functionalization potential to assemble catalytically active proteins, biomaterials, and vaccines onto one nanoparticle in a modular fashion.Graphical

M13 phage: a versatile building block for a highly specific analysis platform.

Viruses are changing the biosensing and biomedicine landscape due to their multivalency, orthogonal reactivities, and responsiveness to genetic modifications. As the most extensively studied phage model for constructing a phage display library, M13 phage has received much research attention as building blocks or viral scaffolds for various applications including isolation/separation, sensing/probing, and in vivo imaging. Through genetic engineering and chemical modification, M13 phages can be functionalized into a multifunctional analysis platform with various functional regions conducting their functionality without mutual disturbance. Its unique filamentous morphology and flexibility also promoted the analytical performance in terms of target affinity and signal amplification. In this review, we mainly focused on the application of M13 phage in the analytical field and the benefit it brings. We also introduced several genetic engineering and chemical modification approaches for endowing M13 with various functionalities, and summarized some representative applications using M13 phages to construct isolation sorbents, biosensors, cell imaging probes, and immunoassays. Finally, current issues and challenges remaining in this field were discussed and future perspectives were also proposed.

Hydrophobization of a TIP60 Protein Nanocage for the Encapsulation of Hydrophobic Compounds.

Encapsulation of hydrophobic molecules in protein-based nanocages is a promising approach for dispersing these molecules in water. Here, we report a chemical modification approach to produce a protein nanocage with a hydrophobic interior surface based on our previously developed nanocage, TIP60. The large pores of TIP60 act as tunnels for small molecules, allowing modification of the interior surface by hydrophobic compounds without nanocage disassembly. We used four different hydrophobic compounds for modification. The largest modification group tested, pyrene, resulted in a modified TIP60 that could encapsulate aromatic photosensitizer zinc phthalocyanine (ZnPC) more efficiently than the other modification compounds. The encapsulated ZnPC generated singlet oxygen upon light activation in the aqueous phase, whereas ZnPC alone formed inert aggregates under the same experimental conditions. Given that chemical modification allows a wider diversity of modifications than mutagenesis, this approach could be used to develop more suitable nanocages for encapsulating hydrophobic molecules of interest.

Crystalline structure of cellulose in wood after chemical modification using cyclic acid anhydrides (maleic and succinic)

The chemical modification of wood can be directed to improve various properties, e.g., the dimensional stability, hardness properties, and/or durability properties, against weathering. In this study, a Romanian softwood species Abies alba Mill. was treated and chemically modified using two cyclic acid anhydrides, i.e., maleic and succinic, to improve its interfacial properties relative to unmodified wood. Structural changes, with focus on the evolution of crystalline part in wood after chemical modification, the water absorption, and the water repellent efficiency, were determined. Maleic anhydride exhibited a lower reactivity towards wood substrate than succinic anhydride, presumably because of their different chemical structure (maleic anhydride is very sensitive to the presence of water). It was found that the percentage of water absorption was diminished, primarily after the succinic anhydride treatment. The chemically modified wood was characterized via Fourier transform-infrared spectroscopy and wide-angle X-ray diffraction methods. The crystalline part from wood structure was evidenced in relation to the employed anhydride in chemical modification approach.

Challenges and progress of chemical modification in piezoelectric composites and their applications

Piezoelectric materials directly convert energy between electrical and mechanical domains, and have been widely employed in electronic devices as sensors and energy harvesters. Recent research endeavors are mainly devoted to dealing with problems such as high stiffness, brittleness, toxicity, poor durability, and low piezoelectric coefficients. Among developed strategies, chemical modification captures much attention. However, the exact physical properties and direct experimental evidence of chemical modification remain elusive or controversial thus far. In this review, we discuss the recently developed piezoelectric modification strategies for piezoelectric composites and assess the effect of different chemical modification approaches on piezoelectric properties. Moreover, we outline existing challenges and new applications of piezoelectric composites.

Green approaches for extraction, chemical modification and processing of marine polysaccharides for biomedical applications.

Over the past few decades, natural-origin polysaccharides have received increasing attention across different fields of application, including biomedicine and biotechnology, because of their specific physicochemical and biological properties that have afforded the fabrication of a plethora of multifunctional devices for healthcare applications. More recently, marine raw materials from fisheries and aquaculture have emerged as a highly sustainable approach to convert marine biomass into added-value polysaccharides for human benefit. Nowadays, significant efforts have been made to combine such circular bio-based approach with cost-effective and environmentally-friendly technologies that enable the isolation of marine-origin polysaccharides up to the final construction of a biomedical device, thus developing an entirely sustainable pipeline. In this regard, the present review intends to provide an up-to-date outlook on the current green extraction methodologies of marine-origin polysaccharides and their molecular engineering toolbox for designing a multitude of biomaterial platforms for healthcare. Furthermore, we discuss how to foster circular bio-based approaches to pursue the further development of added-value biomedical devices, while preserving the marine ecosystem.

The preparation of stable spherical alkali lignin nanoparticles with great thermal stability and no cytotoxicity

In order to further develop the potential applications of lignin biomass, the research on lignin nanoparticles (LNPs) and their nanocomposites has attracted increasing attention. In this study, a facile and no chemical modification approach to prepare stable alkali lignin nanospheres is presented. The nanospheres around 85–125 nm were prepared through the π-π interactions between molecules in the self-assembly process. Lignin alkali was dissolved in ethylene glycol at different initial concentrations and subsequently ultrasound and dialysis treatment were conducted to prepare LNPs. The prepared LNPs had zeta potentials between −20 mV and −40 mV, and they were electrostatically stable over the pH range of 3 to 12 in aqueous solution. The chemical structure of LNPs was not significantly modified compared to lignin. Meanwhile the increased content of carboxyl and aliphatic hydroxyl groups in the LNPs structure was observed. Furthermore, the thermal stability and solubility in organic solvents (ethanol, acetone and THF) of LNPs were enhanced compared to those of lignin. In vitro cell viability evaluation indicated that the prepared LNPs had no cytotoxicity and excellent biocompatibility with mouse fibroblast. Therefore, we proposed here the production of high-quality and renewable LNPs, which will provide a novel perspective for multifunctional applications of bio-based nanomaterials.

Physical, Chemical and Biochemical Modification Approaches of Potato (Peel) Constituents for Bio-Based Food Packaging Concepts: A Review.

Potatoes are grown in large quantities and are mainly used as food or animal feed. Potato processing generates a large amount of side streams, which are currently low value by-products of the potato processing industry. The utilization of the potato peel side stream and other potato residues is also becoming increasingly important from a sustainability point of view. Individual constituents of potato peel or complete potato tubers can for instance be used for application in other products such as bio-based food packaging. Prior using constituents for specific applications, their properties and characteristics need to be known and understood. This article extensively reviews the scientific literature about physical, chemical, and biochemical modification of potato constituents. Besides short explanations about the modification techniques, extensive summaries of the results from scientific articles are outlined focusing on the main constituents of potatoes, namely potato starch and potato protein. The effects of the different modification techniques are qualitatively interpreted in tables to obtain a condensed overview about the influence of different modification techniques on the potato constituents. Overall, this article provides an up-to-date and comprehensive overview of the possibilities and implications of modifying potato components for potential further valorization in, e.g., bio-based food packaging.

Multifunctional Thermal, Acoustic, and Piezoresistive Properties of In Situ-Modified Composite Aerogels with Graphene Oxide as the Main Phase.

Automotive and aerospace industries require advanced materials capable of multifunctional abilities while guaranteeing limited weight and volume and simple processing. Cellular materials such as graphene-based aerogels represent a promising solution. In this study, chemical modification approaches of graphene oxide and polyvinyl alcohol (GOP) aerogels are presented. The combination of a plasticizing agent, glycerol, and a cross-linking agent, glutaraldehyde, is exploited to obtain a mechanically balanced and robust cellular structure. Modified GOP aerogels show high elastic resilience (energy loss coefficient of 29% and compressive strength of 5 kPa at 30% strain, after the 10th compression cycle), low thermal conductivity (0.0424 W mK–1), and high sound absorption (average coefficient of 0.72 between 500 and 1500 Hz) while maintaining a low density of 6.51 kg m–3 with a maximum thickness of 25 mm. Moreover, chemically reduced GOP (rGOP) aerogels are also synthesized. They are characterized by the additional feature of piezoresistive behavior, with only a marginal impact on the other properties. These results show that modified GOP and rGOP aerogels are promising candidates for the fabrication of multifunctional structures to be applied in advanced engineering applications.

Chemical and Physical Approaches for Improved Biopharmaceutical Activity of Amphotericin B: Current and Future Prospective.

Over the last 50 years, the number of patients with mycotic infections has gradually increased. Amphotericin-B is a gold-standard drug used in serious systemic fungal infections. However, limited solubility and permeability are challenging issues associated with Amphotericin-B. Chemical modification is one of the ways to get its broader applicability and improved physicochemical properties. The review article provides a comprehensive overview of the chemical modification approach for investigating the mechanism of action, biological activity, bioavailability, and toxicity of Amphotericin B. Further, several drug delivery approaches have also been utilized to provide better therapeutic outcomes. This gives an overview of chemical approaches for exploring various factors associated with Amphotericin B and information on its drug delivery approaches for improved biopharmaceutical outcomes.

Structural basis of nucleosomal H4K20 methylation by methyltransferase SET8.

Histone H4lysine 20monomethylation (H4K20me1) plays a crucial role in multiple processes including DNA damage repair, DNA replication, and cell cycle control. Histone methyltransferase SET8 (previously named PR-Set7/KMT5A) mediates the chromatin deposition of H4K20me1, but how SET8 recognizes and modifies H4 in the context of the nucleosome is not fully understood. Here, we developed a simple chemical modification approach for H4K20substitution by using the lysine analog S-ethyl-L-cysteine (Ecx). Substitution of H4K20 with H4Ecx20 improves the stability of the SET8-nucleosome complex, allowing us to determine the cryo-EM structure at 3.2Å resolution. Structural analyses show that SET8 directly interacts with the H4 tail and the H2A-H2B acidic patch to ensure nucleosome binding. SET8 residues R339, K341, K351make contact with nucleosomal DNA at the super helical location 2 (SHL2). Substitution of SET8 DNA-binding residues with alanines decreases the SET8-nucleosome interaction and impairs the methyltransferase activity. Disrupting the binding between SET8 R192 and H2A-H2B acidic patch decreases the cellular level of H4K20me1. Together, these results reveal a near-atomic resolution structure of SET8-bound nucleosome and provide insights into the SET8-mediated H4K20 recognition and modification. The lysine-to-Ecx substitution approach can be applied to the study of other methyltransferases.

Recent insight into strategies for the design of antimicrobial peptides (AMPs)

With the increasing development of antibiotic resistance among key bacterial pathogens, there is an urgent need to discover novel classes of antibiotics. Although antimicrobial peptides (AMP) with their specific mode of action are considered major candidates for next-generation antibiotics, several challenges limit the use of these peptides for therapeutic applications. In a large body of research, the focus is given to different approaches to the chemical modification of AMPs and how these modifications may improve the stability, antibiotic activity, proteolytic activity and prevent the cytotoxicity and side effects of AMPs. On the other hand, another group of research investigates the delivery of AMPs via nanocarrier systems as strategies used to enhance stability, control the release of peptides and reduce adverse peptide-related side effects, as well as improve their anti-microbial activities. In the present article, we surveyed most recently published researches that provide us with good knowledge on structural features, mechanism of action, therapeutic aim, advantages and limitations, chemical modification approaches and carrying strategies of AMPs. Finally, according to Quality by Design, the most important potential effective factor and potential risk were mentioned in the development of AMP delivery systems.

Surface Modification of Biomedical Ti and Ti Alloys: A Review on Current Advances.

Ti is widely used as a material for orthopedic implants. As rapid and effective osseointegration is a key factor for the successful application of implants, biologically inert Ti materials start to show inherent limitations, such as poor surface cell adhesion, bioactivity, and bone-growth-inducing capabilities. Surface modification can be an efficient and effective approach to addressing the biocompatibility, mechanical, and functionality issues of the various Ti implant materials. In this study, we have overviewed more than 140 papers to summarize the recent progress in the surface modification of Ti implants by physical and/or chemical modification approaches, aiming at optimizing their wear resistance, biocompatibility, and antimicrobial properties. As an advanced manufacturing technology for Ti and Ti alloys, additive manufacturing was particularly addressed in this review. We also provide an outlook for future research directions in this field as a contribution to the development of advanced Ti implants for biomedical applications.

Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research

Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cell-based product, there appears to be evidence of superior effect and heightened potential success in its expressed vesicles, exosomes, as cell-free products. In addition to their highly desirable intrinsic biologically unique structural, compositional, and morphological characteristics, as well as predominant physiochemical stability and biocompatibility properties, exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. More importantly, the powerful therapeutic potential and superior biological functions of exosomes, particularly, regarding engineered exosomes as cell-free products, and their utilization in a new generation of nanomedicine treatment, vaccination, and diagnosis platforms, brings hope of a change in the near future. This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer.

Protein-RNA interaction guided chemical modification of Dicer substrate RNA nanostructures for superior in vivo gene silencing

Dicer substrate RNA is an alternative gene silencing agent to canonical siRNA. Enhanced in vitro gene silencing can be achieved with RNA substrates by facilitating Ago2 loading of dsRNA after Dicer processing. However, the in vivo use of Dicer substrate RNA has been hindered by its instability and immunogenicity in the body due to the lack of proper chemical modification in the structure. Here, we report a universal chemical modification approach for Dicer substrate RNA nanostructures by optimizing protein-RNA interactions in the RNAi pathway. Proteins involved in the RNAi pathway were utilized for evaluating their recognition and binding of substrate RNA. It was found that conventional chemical modifications could severely affect the binding and processing of substrate RNA, consequently reducing RNAi activity. Protein-RNA interaction guided chemical modification was introduced to RNA nanostructures, and their gene silencing activity was assessed. The optimized RNA nanostructures showed excellent binding and processability with RNA binding proteins and offered the enhancement of in vivo EC50 up to 1/8 of its native form.

Nanocellulose-Based Materials for Water Treatment: Adsorption, Photocatalytic Degradation, Disinfection, Antifouling, and Nanofiltration.

Nanocelluloses are promising bio-nano-materials for use as water treatment materials in environmental protection and remediation. Over the past decades, they have been integrated via novel nanoengineering approaches for water treatment processes. This review aims at giving an overview of nanocellulose requirements concerning emerging nanotechnologies of waster treatments and purification, i.e., adsorption, absorption, flocculation, photocatalytic degradation, disinfection, antifouling, ultrafiltration, nanofiltration, and reverse osmosis. Firstly, the nanocellulose synthesis methods (mechanical, physical, chemical, and biological), unique properties (sizes, geometries, and surface chemistry) were presented and their use for capturing and removal of wastewater pollutants was explained. Secondly, different chemical modification approaches surface functionalization (with functional groups, polymers, and nanoparticles) for enhancing the surface chemistry of the nanocellulose for enabling the effective removal of specific pollutants (suspended particles, microorganisms, hazardous metals ions, organic dyes, drugs, pesticides fertilizers, and oils) were highlighted. Thirdly, new fabrication approaches (solution casting, thermal treatment, electrospinning, 3D printing) that integrated nanocelluloses (spherical nanoparticles, nanowhiskers, nanofibers) to produce water treatment materials (individual composite nanoparticles, hydrogels, aerogels, sponges, membranes, and nanopapers) were covered. Finally, the major challenges and future perspectives concerning the applications of nanocellulose based materials in water treatment and purification were highlighted.

Surface Design of Liquid Separation Membrane through Graft Polymerization: A State of the Art Review.

Surface modification of membranes is an effective approach for imparting unique characteristics and additional functionalities to the membranes. Chemical grafting is a commonly used membrane modification technique due to its versatility in tailoring and optimizing the membrane surface with desired functionalities. Various types of polymers can be precisely grafted onto the membrane surface and the operating conditions of grafting can be tailored to further fine-tune the membrane surface properties. This review focuses on the recent strategies in improving the surface design of liquid separation membranes through grafting-from technique, also known as graft polymerization, to improve membrane performance in wastewater treatment and desalination applications. An overview on membrane technology processes such as pressure-driven and osmotically driven membrane processes are first briefly presented. Grafting-from surface chemical modification approaches including chemical initiated, plasma initiated and UV initiated approaches are discussed in terms of their features, advantages and limitations. The innovations in membrane surface modification techniques based on grafting-from techniques are comprehensively reviewed followed by some highlights on the current challenges in this field. It is concluded that grafting-from is a versatile and effective technique to introduce various functional groups to enhance the surface properties and separation performances of liquid separation membranes.

Inhibition of protein N-myristoylation blocks Plasmodium falciparum intraerythrocytic development, egress and invasion.

We have combined chemical biology and genetic modification approaches to investigate the importance of protein myristoylation in the human malaria parasite, Plasmodium falciparum. Parasite treatment during schizogony in the last 10 to 15 hours of the erythrocytic cycle with IMP-1002, an inhibitor of N-myristoyl transferase (NMT), led to a significant blockade in parasite egress from the infected erythrocyte. Two rhoptry proteins were mislocalized in the cell, suggesting that rhoptry function is disrupted. We identified 16 NMT substrates for which myristoylation was significantly reduced by NMT inhibitor (NMTi) treatment, and, of these, 6 proteins were substantially reduced in abundance. In a viability screen, we showed that for 4 of these proteins replacement of the N-terminal glycine with alanine to prevent myristoylation had a substantial effect on parasite fitness. In detailed studies of one NMT substrate, glideosome-associated protein 45 (GAP45), loss of myristoylation had no impact on protein location or glideosome assembly, in contrast to the disruption caused by GAP45 gene deletion, but GAP45 myristoylation was essential for erythrocyte invasion. Therefore, there are at least 3 mechanisms by which inhibition of NMT can disrupt parasite development and growth: early in parasite development, leading to the inhibition of schizogony and formation of “pseudoschizonts,” which has been described previously; at the end of schizogony, with disruption of rhoptry formation, merozoite development and egress from the infected erythrocyte; and at invasion, when impairment of motor complex function prevents invasion of new erythrocytes. These results underline the importance of P. falciparum NMT as a drug target because of the pleiotropic effect of its inhibition.

Recent Advances on Cellulose Nanocrystals and Their Derivatives.

Nanocellulose, typically cellulose nanocrystals (CNCs), has excellent properties and is widely used. In particular, CNC has a small dimension, high chemical reactivity, and high sustainability, which makes it an excellent candidate as a starting material to be converted into nanocellulose derivatives. Chemical modification is essential for obtaining the desired products; the modifications create different functional attachment levels and generate novel microstructures. Recent advances on nanocellulose derivatives have not yet been reviewed and evaluated for the last five years. Nanocellulose derivative materials are being used in a wide variety of high-quality functional applications. To meet these requirements, it is essential for researchers to fully understand CNCs and derivative materials, precisely their characteristics, synthesis methods, and chemical modification approaches. This paper discusses CNC and its derivatives concerning the structural characteristics, performance, and synthesis methods, comparing the pros and cons of these chemical modification approaches reported in recent years. This review also discusses the critical physicochemical properties of CNC derivative products, including solubility, wetting performance, and associated impacts on properties. Lastly, this paper also comments on the bottlenecks of nanocellulose derivatives in various applications and briefly discusses their future research direction.

Recent Advances in Modification Approaches, Health Benefits, and Food Applications of Resistant Starch

AbstractResistant starch (RS) is a non‐digestible carbohydrate that has numerous biological benefits. However, the amounts of RS are limited in most native cereal starches, thus developing RS‐fortified starch sources and food products is necessary. This review summarizes the effectiveness of RS improvement by chemical, enzymatic, and physical modification approaches in starches from various origins. The functions of RS in regulating the metabolisms and the influences of RS on the nutritional and textural properties of various foods are also elucidated. After modification, the molecular structures are altered and the starch granules became more resistant to enzymatic digestion. However, the comparison of the RS contents between raw and cooked starch is absent in many studies. In addition, RS plays an essential role in attenuating postprandial glycemia, inhibiting glucose and lipid synthesis and promoting glucose tolerance, insulin sensitivity, and lipid degradation, which are controlled by the enriched diversity and abundance of the beneficial microbiota in the colon, together with more short‐chain fatty acids. The incorporation of RS in food products significantly increases nutritional value without unacceptable quality loss, which provides a new direction for manufacturing functional foods.