Synthetic Strategies for the Biotinylation of Bioactive Small Molecules

Biotinylation, the functional appendage of a biotin moiety to a bioactive compound (including small molecules and biological macromolecules), represents a common technique for identification of the intracellular binding partners that underlie the foundation of observed biological activity. Introduction of an attachment tether to the framework of a compound of interest must be planned at an early stage of development, and many considerations apply: 1) region of attachment, so as not to impede the pharmacophore; 2) stability of the parent molecular architecture to biotinylation conditions; 3) regioselectivity for the chosen tethering location over other reactive functionalities; 4) toxicity of reagents if biotinylation is to be performed in vitro; and 5) overall ease of synthesis. This review is intended to serve as a guide for the selection of appropriate tethering modalities. Examples of the common techniques used to affix biotin, including amide bond formation, [3+2] cycloadditions through “click” chemistry, Staudinger ligation, and thioether formation will be discussed, along with analysis of the wider applications of synthetic methodology that have been applied toward the biotinylation of small molecules.     

Polymers used to influence cell fate in 3D geometry: New trends

The extracellular matrix (ECM) is a hydrogel-like structure comprised of several different biopolymers, encompassing a wide range of biological, chemical, and mechanical properties. The composition, organization, and assembly of the ECM play a critical role in cell function. Cellular behavior is guided by interactions that occur between cells and their local microenvironment, and this interrelationship plays a significant role in determining physiological functions. Bioengineering approaches have been developed to mimic native tissue microenvironments by fabricating novel bioactive hydrogel scaffolds. This review explores material designs and fabrication approaches that are guiding the design of hydrogels as tissue engineered scaffolds. As the fundamental biology of the cellular microenvironment is often the inspiration for material design, the review focuses on modifications to control bioactive cues such as adhesion molecules and growth factors, and summarizes the current applications of biomimetic scaffolds that have been used in vitro as well as in vivo.     

Hybrids as NO Donors

Cinnamic acid and its derivatives have been studied for a variety of biological properties, including anti-inflammatory, antioxidant, anticancer, antihypertensive, and antibacterial. Many hybrids of cinnamic derivatives with other bioactive molecules have been synthesized and evaluated as nitric oxide (NO) donors. Since NO plays a significant role in various biological processes, including vasodilation, inflammation, and neurotransmission, NO donor groups are incorporated into the structures of already-known bioactive molecules to enhance their biological properties. In this review, we present cinnamic hybrids with NO-donating ability useful in the treatment of several diseases.     

Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules in live cells and in vivo

The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases,such as cancer and neurodegenerative and cardiovascular diseases.Therefore,the simultaneous,accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases.Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and in vivo due to its excellent performances,including high sensitivity and selectivity,noninvasive properties,real-time and high spatial temporal resolution.Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems.Hence,in this review,we focus on summarizing the design strategies,classifications,and bioimaging applications of dual-response fluorescent probes over the past decade.Furthermore,future research directions in this field are proposed.     

Bioactive Compounds During Drying of Chili Peppers

Chili pepper (Capsicum annuum L.) is one of the most popular fresh vegetables or ingredients (condiments) that provide natural flavor and color. Its color is provided by carotenoids and its flavor is provided by capsaicinoids, which are considered bioactive compounds due to their beneficial effect on health. Moreover, the chili pepper also contains other bioactive compounds, such as phenols and vitamin C. The main process for its preservation and marketing is drying, during which bioactive compounds can be degraded. This review describes the effect of drying on the bioactive compounds of chili peppers using conventional and unconventional technologies.     

Bioactive Molecules in Soil Ecosystems: Masters of the Underground

Complex biological and ecological processes occur in the rhizosphere through ecosystem-level interactions between roots, microorganisms and soil fauna. Over the past decade, studies of the rhizosphere have revealed that when roots, microorganisms and soil fauna physically contact one another, bioactive molecular exchanges often mediate these interactions as intercellular signal, which prepare the partners for successful interactions. Despite the importance of bioactive molecules in sustainable agriculture, little is known of their numerous functions, and improving plant health and productivity by altering ecological processes remains difficult. In this review, we describe the major bioactive molecules present in below-ground ecosystems (i.e., flavonoids, exopolysaccharides, antibiotics and quorum-sensing signals), and we discuss how these molecules affect microbial communities, nutrient availability and plant defense responses.     

Chondroitin sulfate: extraction,purification, microbial and chemical synthesis

Chondroitin sulfate, a type of acid mucopolysaccharide possessing a variety of bioactivities, has attracted tremendous interest due to its use in the relief of joint diseases. It has been widely applied in different fields, such as medicine, biotechnology, pharmacy, textiles, food and cosmetics. This mini‐review focuses on the main methods of its extraction and purification, and recent advances in bio‐syntheses and chemical synthesis of such molecules. In addition, further studies in these aspects are proposed based on current research. © 2014 Society of Chemical Industry     

Natural and Genetically Engineered Proteins for Tissue Engineering

To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio-resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials.In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein-based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification.     

Basic Methods for Preparation of Liposomes and Studying Their Interactions with Different Compounds,with the Emphasis on Polyphenols

Studying the interactions between lipid membranes and various bioactive molecules (e.g., polyphenols) is important for determining the effects they can have on the functionality of lipid bilayers. This knowledge allows us to use the chosen compounds as potential inhibitors of bacterial and cancer cells, for elimination of viruses, or simply for keeping our healthy cells in good condition. As studying those effect can be exceedingly difficult on living cells, model lipid membranes, such as liposomes, can be used instead. Liposomal bilayer systems represent the most basic platform for studying those interactions, as they are simple, quite easy to prepare and relatively stable. They are especially useful for investigating the effects of bioactive compounds on the structure and kinetics of simple lipid membranes. In this review, we have described the most basic methods available for preparation of liposomes, as well as the essential techniques for studying the effects of bioactive compounds on those liposomes. Additionally, we have provided details for an easy laboratory implementation of some of the described methods, which should prove useful especially to those relatively new on this research field.     

Whole Alga,Algal Extracts,and Compounds as Ingredients of Functional Foods: Composition and Action Mechanism Relationships in the Prevention and Treatment of Type-2 Diabetes Mellitus

Type-2 diabetes mellitus (T2DM) is a major systemic disease which involves impaired pancreatic function and currently affects half a billion people worldwide. Diet is considered the cornerstone to reduce incidence and prevalence of this disease. Algae contains fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential antidiabetic activity. This review delves into the applications of algae and their components in T2DM, as well as to ascertain the mechanism involved (e.g., glucose absorption, lipids metabolism, antioxidant properties, etc.). PubMed, and Google Scholar databases were used. Papers in which whole alga, algal extracts, or their isolated compounds were studied in in vitro conditions, T2DM experimental models, and humans were selected and discussed. This review also focuses on meat matrices or protein concentrate-based products in which different types of alga were included, aimed to modulate carbohydrate digestion and absorption, blood glucose, gastrointestinal neurohormones secretion, glycosylation products, and insulin resistance. As microbiota dysbiosis in T2DM and metabolic alterations in different organs are related, the review also delves on the effects of several bioactive algal compounds on the colon/microbiota-liver-pancreas-brain axis. As the responses to therapeutic diets vary dramatically among individuals due to genetic components, it seems a priority to identify major gene polymorphisms affecting potential positive effects of algal compounds on T2DM treatment.     

可见光催化构建碳氮键的研究进展

可见光是一种清洁的可再生能源,利用可见光代替传统的热能进行化学转化具有绿色、高效的优点.碳氮键是广泛存在于多种生物活性分子和药物分子中的重要化学键,光催化构筑碳氮键在有机和药物化学领域中具有重要研究意义.近年来光催化形成碳氮键研究得到了快速发展,许多新颖的合成方法不断涌现.综述了可见光催化构建C(sp2)—N键和C(s...     

Functionalization of polymer multilayer thin films for novel biomedical applications

The design of functional polymer multilayer thin films with nanometer scale control is of great interest for biomedical applications such as tissue engineering, targeted drug delivery, controlled release system, and regenerative medicine. Various functions and properties of polymer thin films can be easily programmed and realized by the layer-by-layer assembly strategy, which is a facile and versatile deposition method to prepare well-defined biomedical multilayer platforms due to its benign process to prepare films under mild conditions and the capability of incorporating bioactive materials at a desired location within the films. Particularly, the fine tuning of physicochemical and biological properties of multilayer thin films is significantly important for designing novel biomedical platforms capable of adjusting the cellular functions. In this review, we focus on the overall background of the layer-by-layer assembly as well as the tuning of multilayer film properties and the programming of biological functions into the polymer thin films with a view on the control of cellular functions. Furthermore, we highlighted the recent achievements toward the design of novel biomedical platforms based on functionalized polymer multilayer thin films.     

Fruit Extract Mediated Green Synthesis of Metallic Nanoparticles: A New Avenue in Pomology Applications

Fruit extracts have natural bioactive molecules that are known to possess significant therapeutic potential. Traditionally, metallic nanoparticles were synthesized via chemical methods, in which the chemical act as the reducing agent. Later, these traditional metallic nanoparticles emerged as the biological risk, which prompted researchers to explore an eco-friendly approach. There are different eco-friendly methods employed for synthesizing these metallic nanoparticles via the usage of microbes and plants, primarily via fruit extract. These explorations have paved the way for using fruit extracts for developing nanoparticles, as they eliminate the usage of reducing and stabilizing agents. Metallic nanoparticles have gained significant attention, and are used for diverse biological applications. The present review discusses the potential activities of phytochemicals, and it intends to summarize the different metallic nanoparticles synthesized using fruit extracts and their associated pharmacological activities like anti-cancerous, antimicrobial, antioxidant and catalytic efficiency.     

Calcium zirconium silicate (baghdadite) ceramic as a biomaterial

Bioceramics have been widely used for many years to restore and replace hard tissues including bones, teeth and mineralized matrices such as calcified cartilages at osteochondral interfaces, mainly because of their physicochemical similarity with these tissues. Calcium silicate based bioceramics have been shown to possess high bioactivity due to having high apatite-forming ability and stimulating cell proliferation, as well as biodegradability at rates appropriate to hard tissue regeneration. The outstanding biological properties of these ceramics have made them the most studied hard tissue engineering biomaterials along with calcium phosphates and bioactive glasses. Baghdadite is a calcium silicate containing zirconium ions which promotes the proliferation and differentiation of human osteoblasts and consequently increases mineral metabolism and ossification. Recently, it has attracted considerable attention in academic community and widely studied in the form of porous scaffolds, coatings, bone cement and void fillers, microspheres and nanoparticles mostly in orthopedic, dental and maxillofacial applications. This review paper is aimed to summarize and discuss the most relevant studies on the mechanical properties, apatite formation ability, dissolution behavior, and in vitro and in vivo biological properties of baghdadite as a biomaterial for hard tissue regeneration applications.     

喹啉及其衍生物的合成与生物活性研究进展

喹啉及其衍生物具有广泛的生物活性如抗HIV、抗癌、抗病毒及杀菌等,显示了广泛的应用前景。综述了近年来喹啉及其衍生物的合成方法及生物活性的研究进展。     

δ-Mercaptolysine Assisted Ubiquitination

The field of chemical biology of ubiquitin is gaining significant interest in recent years due to the diversity and complexity of the ubiquitin signal in numerous biological functions in eukaryotes. The inability of biological methods to prepare ubiquitinated peptides and proteins with full control over the ubiquitination sites, types, and lengths of the ubiquitin chains is one of the main challenges in the ongoing efforts to fully understand the ubiquitin signal at the molecular level. This has been a major driving force for the development of chemical tools to complement biological methods in preparing ubiquitin bioconjugates for various biochemical and structural studies. This review deals with the recent advances in developing chemical methods for the synthesis of ubiquitinated peptides and proteins assisted by δ-mercaptolysine, which enable isopeptide formation in a highly efficient and chemoselective manner.     

Strategies in biomimetic surface engineering of nanoparticles for biomedical applications

Engineered nanoparticles (NPs) play an increasingly important role in biomedical sciences and in nanomedicine. Yet, in spite of significant advances, it remains difficult to construct drug-loaded NPs with precisely defined therapeutic effects, in terms of release time and spatial targeting. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Upon injection in the blood stream or following oral administation, NPs have to bypass numerous barriers prior to reaching their intended target. A particularly successful design strategy consists in masking the NP to the biological environment by covering it with an outer surface mimicking the composition and functionality of the cell's external membrane. This review describes this biomimetic approach. First, we outline key features of the composition and function of the cell membrane. Then, we present recent developments in the fabrication of molecules that mimic biomolecules present on the cell membrane, such as proteins, peptides, and carbohydrates. We present effective strategies to link such bioactive molecules to the NPs surface and we highlight the power of this approach by presenting some exciting examples of biomimetically engineered NPs useful for multimodal diagnostics and for target-specific drug/gene delivery applications. Finally, critical directions for future research and applications of biomimetic NPs are suggested to the readers.     

Bioapplications of light‐sensitive polymer films and capsules assembled using the layer‐by‐layer technique

This review covers the area of bioapplications of layer‐by‐layer assembled polymer planar films and microcapsules—biologically relevant responses stimulated by light. We present recent progress in light‐stimulated release of bioactive molecules from the assembled structures. Functionalization of the films with metal nanoparticles and bioactive molecules that provide the films with light sensitivity and reservoir properties is also described. The use of these films in the delivery of bioactive molecules is closely related to light‐induced cargo release from capsules; this promising method of intracellular delivery is also addressed. Copyright © 2012 Society of Chemical Industry     

Lipid Metabolism,Apoptosis and Cancer Therapy

Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.     

Imidazole- and imidazolium-containing polymers for biology and material science applications

The imidazole ring is ubiquitous in nature and imidazole functionality plays a critical role in many structures within the human body, notably as histamine and histadine. Imidazoles offer many biophysical interactions including their ability to hydrogen bond with drugs and proteins. In contrast, imidazolium salts have lost their strong hydrogen-bonding ability through alkylation of both nitrogens, but they are able to aggregate electrostatically. Imidazolium salts are used to extract metal ions from aqueous solutions, dissolve carbohydrates, create polyelectrolyte brushes on surfaces, coat metal nanoparticles, provide antimicrobial action, and create oriented liquid crystals. Bioactive applications include imidazolium hydrogels, antiarrhythmics, and anti-metastic agents. This review will describe the synthesis and design of imidazole derivatives and imidazolium-containing polymers as bioactive materials. Imidazole-based polymers readily associate with biological molecules through hydrogen-bonding, and imidazolium analogs offer electrostatic interactions, aggregation, and self-assembly. Design of novel imidazole- and imidazolium-based macromolecules remains as an exciting and emerging field.