dendrons
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In this work, a unique high-performance liquid chromatographic method was developed and applied for monitoring the synthesis of polyethyleneglycol surface modified poly(amidoamine) cystamine core dendrimers (PEG-PAMAMs) and PEG-PAMAM-alkynes with a single alkyne moiety attached to the core of a dendron through a unique sulfhydryl group. The separation of the products was performed on a column with a pentafluorphenylpropyl stationary phase, allowing multiple mechanisms of selectivity. More than 50 peaks were separated in one run, reflecting the degree of dendrimer PEGylation (PEG average molecular mass: 3,000). Moreover, modification of PAMAM with a single alkyne group could be distinguished. The developed method can be used for the general characterization and separation of PAMAM derivatives, in which the degree of modification is critical for final applications.
Over the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective antimicrobial molecules. On the one hand, antimicrobial peptides (AMPs) are regarded as good alternatives because of their generally broad-spectrum activities, but sometimes they can be easily degraded by the organism or be toxic to animal cells. On the other hand, cationic carbosilane dendrons, whose focal point can be functionalized in many different ways, have also shown good antimicrobial activity. In this work, we synthetized first- and second-generation cationic carbosilane dendrons with a maleimide molecule on their focal point, enabling their functionalization with three different AMPs. After different microbiology studies, we found an additive effect between first-generation dendron and AMP3 whose study reveals three interesting effects: (i) bacteria aggregation due to AMP3, which could facilitate bacteria detection or even contribute to antibacterial activity by preventing host cell attack, (ii) bacteria disaggregation capability of second-generation cationic dendrons, and (iii) a higher AMP3 aggregation ability when dendrons were added previously to peptide treatment. These compounds and their different effects observed over bacteria constitute an interesting system for further mechanism studies.
Bile acids are compounds with many functions in liver and other parts of gastrointestinal tract. Apart from long-known ability of bile acids to form micelles and help with both intestinal digestion and absorption of lipids, other (but not less important) properties of these molecules are still neglected. Among pleitropic effects of bile acids belong regulation of cholesterol homeostasis, antimicrobial properties and novel functions discovered in last decades. It seems that the notion of bile acids as compounds important mainly for their physico-chemical properties should be reevaluated and we have to put stress on the importance of bile acids as structures with hormonal functions. Moreover, the molecules of bile acids have unusual properties, which predetermine them for attractive drug designs, as vectors for delivery of active substances, production of chiral compounds, dendrons, or even photoresistant molecules for microcircuits.
- MeSH
- antivirové látky MeSH
- biologické markery MeSH
- dendrimery MeSH
- kationické antimikrobiální peptidy izolace a purifikace MeSH
- nanočástice MeSH
- nosiče léků MeSH
- Squalus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- žlučové kyseliny a soli * farmakologie metabolismus terapeutické užití MeSH
- Publikační typ
- práce podpořená grantem MeSH
V poslední době lze pozorovat velký rozvoj částicových lékových forem. Některé z nich, např. pelety, mikročástice a lipozomy, našly ve farmakoterapii již své uplatnění. Na jiné, zejména tzv. chytré nanočástice schopné reagovat na různé stimuly, využití teprve čeká. „Chytré“ nano- a mikročástice jsou předmětem zájmu mnoha různých oborů: chemických věd, životního prostředí, biotechnologie, medicíny a farmaceutického průmyslu. Nacházejí uplatnění v grafickém umění, zemědělství, výpočetní technice (elektronický inkoust) apod. Nanotechnologie, související s mikroelektronikou a rozvojem výpočetní techniky, představují významný stupeň ve vývoji vědy a technologií, kde se překrývají objevy v biologii, diagnostice, terapii, mikroelektronice, počítačovém inženýrství a v oblasti vývoje syntetických polymerů. Článek seznamuje s nejdůležitějšími typy farmaceuticky využitelných nanočásticových systémů a s některými jejich pomocnými látkami.
In recent years a great development of multiparticulate dosage forms can be observed. Some of them, e.g. pellets, microparticles and liposomes, are already used in pharmacotherapy. The others, especially so called smart nanoparticles responsive or sensitive to specific stimuli will find their use in next future. Smart nano- and microparticles are in current potential interest in many different areas of chemical and life sciences, biotechnology, medicine and pharmaceutical industry. They already found their application in graphic art, agriculture, computer science (electronic ink) etc. Nanotechnologies related to microelectronics and computers represent a great step of science and technology that overlaps many other developments in biology, diagnostic and therapeutic medicine, microelectronics, computer-aided engineering and synthetic polymers. The article is focused on most important nanoparticulate systems of possible pharmaceutical use and some of their excipients.
Cancer is one of the most important problems of modern medicine. At the present time, gene therapy has been developed against cancer, which includes the delivery of anticancer small interfering RNAs (siRNAs) directed at cancer proteins. The prospect of creating drugs based on RNA interference implies the use of delivery systems. Metal nanoparticles are the most studied objects for medicine, including their application as non-viral vectors. We have synthesized gold nanoparticles (AuNPs) modified with cationic carbosilane dendrons of 1-3 generations, with a positive charge on the surface, gold nanoparticles can effectively bind small interfering RNAs. Using a photometric viability test and flow cytometry, we assessed the ability of dendronized gold nanoparticles in delivering siRNAs to tumor cells. The efficiency of the complexes in initiating apoptosis was measured and, also, the overall effect of proapoptotic siRNA on cells. AuNP15 has both the highest efficacy and toxicity. The delivery efficiency in suspension cell lines was 50-60%. Complexes with targeted siRNA decreased cell viability by 20% compared to control and initiated apoptosis.
- Publikační typ
- časopisecké články MeSH
Nanomaterials are in analytical science used for a broad range of purposes, covering the area of sample pretreatment as well as separation, detection, and identification of target molecules. This part of the review covers capillary electrophoresis (CE) of nanomaterials and focuses on the application of CE as a method for characterization used during nanomaterial synthesis and modification as well as the monitoring of their properties and interactions with other molecules. The heterogeneity of the nanomaterial family is extremely large. Depending on different definitions of the term Nanomaterial/Nanoparticle, the group may cover metal and polymeric nanoparticles, carbon nanomaterials, liposomes and even dendrimers. Moreover, these nanomaterials are usually subjected to some kind of surface modification or functionalization, which broadens the diversity even more. Not only for purposes of verification of nanomaterial synthesis and batch-to-batch quality check, but also for determination the polydispersity and for functionality characterization on the nanoparticle surface, has CE offered very beneficial capabilities. Finally, the monitoring of interactions between nanomaterials and other (bio)molecules is easily performed by some kind of capillary electromigration technique.
The size of information that can be stored in nucleic acids, proteins, and carbohydrates was calculated. The number of hexamers for peptides is 64,000,000 (20(6)) and seems to be impressive in comparison with 4,096 (4(6)) hexanucleotides, but the number of isomers of hexasaccharides is 1.44 × 10(15). Carbohydrates are therefore the best high-density coding system. This language has been named glycocode resp. sugar code. In comparison with peptide dendrimers, the amount of information carried by glycopeptide dendrimers or glycodendrimers is therefore much higher. This is reflected by the variability of structures and functions (activities). This review is about the broad area of peptide and glycopeptide dendrimers. The dendrimeric state and physicochemical properties and general consequences are described, together with a cluster effect. The impact of cluster effect to biological, chemical, and physical properties is discussed. Synthesis of dendrimers by convergent and divergent approaches, "Lego" chemistry, ligation strategies, and click chemistry is given with many examples. Purification and characterization of dendrimers by chromatographic methods, electromigration methods, and mass spectrometry are briefly mentioned. Different types of dendrimers with cyclic core, i.e. RAFTs, TASPs and analogous cyclic structures, carbopeptides, carboproteins, octopus glycosides, inositol-based dendrimers, cyclodextrins, calix[4]arenes, resorcarenes, cavitands, and porphyrins are given. Dendrimers can be used for creation of libraries, catalysts, and solubilizing agents. Biocompatibility and toxicity of dendrimers is discussed, as well as their applications in nanoscience, nanotechnology, drug delivery, and gene delivery. Carbohydrate interactions of glycopeptide dendrimers (bacteria, viruses, and cancer) are described. Examples of dendrimers as anti-prion agents are given. Dendrimers represent a fast developing area which partly overlaps with nanoparticles and nanotechnologies.
- MeSH
- dendrimery chemie MeSH
- farmakoterapie přístrojové vybavení MeSH
- genový targeting přístrojové vybavení MeSH
- glykopeptidy chemie MeSH
- lékové transportní systémy přístrojové vybavení MeSH
- lidé MeSH
- nanotechnologie přístrojové vybavení MeSH
- peptidy chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
This review focuses on analytical techniques used for separation and characterization of dendrimers and their derivatives. These macromolecules have been attractive material for a development of new drug carriers and imaging agents. They are also interesting for many biological and industrial applications. The review mentions a few of them.
Utilization of metallic nanoparticles in various biotechnological and medical applications represents one of the most extensively investigated areas of the current materials science. These advanced applications require the appropriate chemical functionalization of the nanoparticles with organic molecules or their incorporation in suitable polymer matrices. The intensified interest in polymer nanocomposites with silver nanoparticles is due to the high antimicrobial effect of nanosilver as well as the unique characteristics of polymers which include their excellent structural uniformity, multivalency, high degree of branching, miscellaneous morphologies and architectures, and highly variable chemical composition. In this review, we explore several aspects of antimicrobial polymer silver nanocomposites, giving special focus to the critical analysis of the reported synthetic routes including their advantages, drawbacks, possible improvements, and real applicability in antibacterial and antifungal therapy. A special attention is given to "green" synthetic routes exploiting the biopolymeric matrix and to the methods allowing preparing magnetically controllable antimicrobial polymers for targeting to an active place. The controversial mechanism of the action of silver against bacteria, fungi and yeasts as well as perspectives and new applications of silver polymeric nanocomposites is also briefly discussed.
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- dendrimery chemie MeSH
- kovové nanočástice MeSH
- nanokompozity chemie klasifikace MeSH
- polymery chemie MeSH
- sacharidy chemie MeSH
- stříbro chemie MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The scope of this two-part review is to summarize publications dealing with CE and nanomaterials together. This topic can be viewed from two broad perspectives, and this article is trying to highlight these two approaches: (i) CE of nanomaterials, and (ii) nanomaterials in CE. The second part aims at summarization of publications dealing with application of nanomaterials for enhancement of CE performance either in terms of increasing the separation resolution or for improvement of the detection. To increase the resolution, nanomaterials are employed as either surface modification of the capillary wall forming open tubular column or as additives to the separation electrolyte resulting in a pseudostationary phase. Moreover, nanomaterials have proven to be very beneficial for increasing also the sensitivity of detection employed in CE or even they enable the detection (e.g., fluorescent tags of nonfluorescent molecules).
- MeSH
- dendrimery chemie MeSH
- elektroforéza kapilární přístrojové vybavení metody MeSH
- elektrolyty chemie MeSH
- fluorescenční barviva analýza MeSH
- liposomy chemie MeSH
- nanostruktury chemie MeSH
- nanotrubičky uhlíkové chemie MeSH
- povrchové vlastnosti MeSH
- senzitivita a specificita MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
