116 research outputs found
Alginate Blocks and Block Polysaccharides: A Review
AbstractAlginates consist of distinct blocks with different physical properties. This short review focuses on research carried out in Trondheim related to the early discovery of the block structure, their isolation, their different chemical and physical properties, and how they recently are utilized in diblock polysaccharides to obtain new nanostructuring properties
Alginate-based diblock polymers: preparation, characterization and Ca-induced self-assembly
Renewable resources can provide a range of different polysaccharide blocks that can be used to prepare new types of stimuli-responsive polysaccharide-based block copolymers. Alginates are natural polysaccharides widely used as biomaterials. Functional properties depend on the content and distribution of the two 4-linked monomers (β-D-mannuronate (M) and α-L-guluronate (G)). Blocks of L-guluronate (Gn) are responsible for cooperative binding of calcium ions and hydrogel formation. Incorporation of such blocks in block polysaccharide copolymers would represent a new class of engineered, Ca-sensitive biomacromolecules. Dioxyamines and dihydrazides have recently been shown to be well suited for preparation of block polysaccharide structures. Here we first show that when applied to alginate blocks (Gn and Mn) the two types are both very reactive, but the detailed distribution of acyclic (E)- and (Z)-forms and cyclic N-pyranosides, reaction kinetics, conjugate stability, and the rate of Schiff base reduction with α-picoline borane differ considerably, also compared to other polysaccharides. Hence, alginate specific protocols were developed. The linkers introduce a highly flexible joint in otherwise semiflexible Gn-based diblocks. This was demonstrated by SEC-MALS using a symmetrical Gn-b-Gn diblock, which in solution can best be described according to a broken rod model. Ca-Induced self-assembly of Gn-b-dextran diblocks was studied by dynamic light scattering, demonstrating that well defined nanoparticles could be prepared for certain combinations of chain lengths. Taken together, this approach provides a new class of engineered, stimuli-responsive block polysaccharide copolymers solely based on natural resources
RSC Adv.
Developing new biomaterials is an active research area owing to their applications in regenerative medicine, tissue engineering and drug delivery. Elastin-like polypeptides (ELPs) are good candidates for these applications because they are biosourced, biocompatible and biodegradable. With the aim of developing ELP-based micelles for drug delivery applications we have synthesized 15 acyl-ELP compounds by conjugating myristic, palmitic, stearic, oleic or linoleic acid to the N-terminus of three ELPs differing in molar mass. The ELP-fatty acid conjugates have interesting solution behavior. They form micelles at low temperatures and aggregate above the cloud point temperature (Tcp). The critical micelle concentration depends on the fatty acid nature while the micelle size is mainly determined by the ELP block length. We were able to show that ELPs were better hydrated in the micelles than in their individual state in solution. The micelles are stable in phosphate-buffer saline at temperatures below the Tcp, which can vary between 20 °C and 38 °C depending on the length or hydrophilicity of the ELP. Acyl-ELP micelles were loaded with the small hydrophobic molecule Nile red. The encapsulation efficiency and release kinetics showed that the best loading conditions were achieved with the largest ELP conjugated to stearic acid
The genetic and epigenetic landscape of the Arabidopsis centromeres.
Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by complex repeats. We used longread sequencing to generate the Col-CEN Arabidopsis thaliana genome assembly that resolves all five centromeres. The centromeres consist of megabase-scale tandemly repeated satellite arrays, which support CENH3 occupancy and are densely DNA methylated, with satellite variants private to each chromosome. CENH3 preferentially occupies satellites that show least divergence and occur in higherorder repeats. The centromeres are invaded by ATHILA retrotransposons, which disrupt genetic and epigenetic organization. Centromeric crossover recombination is suppressed, yet low levels of meiotic DSBs occur that are regulated by DNA methylation. We propose that Arabidopsis centromeres are evolving via cycles of satellite homogenization and retrotransposon-driven diversification.BBSRC grants BB/S006842/1, BB/S020012/1 and BB/V003984/1
Temperature-induced melting of double-stranded DNA in the absence and presence of covalently bonded antitumour drugs: insight from molecular dynamics simulations
The difference in melting temperature of a double-stranded (ds) DNA molecule in the absence and presence of bound ligands can provide experimental information about the stabilization brought about by ligand binding. By simulating the dynamic behaviour of a duplex of sequence 5′-d(TAATAACGGATTATT)·5′-d(AATAATCCGTTATTA) in 0.1 M NaCl aqueous solution at 400 K, we have characterized in atomic detail its complete thermal denaturation profile in <200 ns. A striking asymmetry was observed on both sides of the central CGG triplet and the strand separation process was shown to be strongly affected by bonding in the minor groove of the prototypical interstrand crosslinker mitomycin C or the monofunctional tetrahydroisoquinolines trabectedin (Yondelis®), Zalypsis® and PM01183®. Progressive helix unzipping was clearly interspersed with some reannealing events, which were most noticeable in the oligonucleotides containing the monoadducts, which maintained an average of 6 bp in the central region at the end of the simulations. These significant differences attest to the demonstrated ability of these drugs to stabilize dsDNA, stall replication and transcription forks, and recruit DNA repair proteins. This stabilization, quantified here in terms of undisrupted base pairs, supports the view that these monoadducts can functionally mimic a DNA interstrand crosslink
Analysis of BAC end sequences in oak, a keystone forest tree species, providing insight into the composition of its genome
<p>Abstract</p> <p>Background</p> <p>One of the key goals of oak genomics research is to identify genes of adaptive significance. This information may help to improve the conservation of adaptive genetic variation and the management of forests to increase their health and productivity. Deep-coverage large-insert genomic libraries are a crucial tool for attaining this objective. We report herein the construction of a BAC library for <it>Quercus robur</it>, its characterization and an analysis of BAC end sequences.</p> <p>Results</p> <p>The <it>Eco</it>RI library generated consisted of 92,160 clones, 7% of which had no insert. Levels of chloroplast and mitochondrial contamination were below 3% and 1%, respectively. Mean clone insert size was estimated at 135 kb. The library represents 12 haploid genome equivalents and, the likelihood of finding a particular oak sequence of interest is greater than 99%. Genome coverage was confirmed by PCR screening of the library with 60 unique genetic loci sampled from the genetic linkage map. In total, about 20,000 high-quality BAC end sequences (BESs) were generated by sequencing 15,000 clones. Roughly 5.88% of the combined BAC end sequence length corresponded to known retroelements while <it>ab initio </it>repeat detection methods identified 41 additional repeats. Collectively, characterized and novel repeats account for roughly 8.94% of the genome. Further analysis of the BESs revealed 1,823 putative genes suggesting at least 29,340 genes in the oak genome. BESs were aligned with the genome sequences of <it>Arabidopsis thaliana</it>, <it>Vitis vinifera </it>and <it>Populus trichocarpa</it>. One putative collinear microsyntenic region encoding an alcohol acyl transferase protein was observed between oak and chromosome 2 of <it>V. vinifera.</it></p> <p>Conclusions</p> <p>This BAC library provides a new resource for genomic studies, including SSR marker development, physical mapping, comparative genomics and genome sequencing. BES analysis provided insight into the structure of the oak genome. These sequences will be used in the assembly of a future genome sequence for oak.</p
Two Non-covalent Methods to Decorate Nanoparticles with Block Copolymers
The physical adsorption of block copolymers is a simple and reliable approach to functionalize the surface of organic or inorganic nanoparticles. This article presents two novel methods of particle coating with block copolymers that may apply to various aqueous colloidal dispersions. The first method relies on the use of charged block copolymers having two adsorbing blocks, which can adopt a typical anchor-buoy conformation at the particle surface when proper conditions are used. The second approach consists of self-assembling a bilayer of amphiphilic block copolymers around charged nanoparticles. In both cases, a special emphasis is placed on the process used to control and orient the molecular interactions between the copolymer and the particles
Fundamental and Practical Aspects in the Formulation of Colloidal Polyelectrolyte Complexes of Chitosan and siRNA
The formation of electrostatic interactions between polyanionic siRNA and polycations gives an easy access to the formation of colloidal particles capable of delivering siRNA in vitro or in vivo. Among the polycations used for siRNA delivery, chitosan occupies a special place due to its unique physicochemical and biological properties. In this chapter we describe the fundamental and practical aspects of the formation of colloidal complexes between chitosan and siRNA. The basis of the electrostatic complexation between oppositely charged polyelectrolytes is first introduced with a focus on the specific conditions to obtain stable colloid complex particles. Subsequent, the properties that make chitosan so special are described. In a third part, the main parameters influencing the colloidal properties and stability of siRNA/chitosan complexes are reviewed with emphasis on some practical aspects to consider in the preparation of complexes
Chitosane (comportement en solution et formation de particules)
Le chitosane est un polysaccharide soluble en milieux aqueux par protonation de ses fonctions amine. La première partie de ce travail présente une étude assez détaillée du comportement du chitosane en solution en fonction du degré d'acétylation et du degré de neutralisation des fonctions amine. L'utilisation de différentes techniques analytiques telles que la diffusion statique de la lumière a permis de décrire la conformation du chitosane et d'établir une loi de comportement. La deuxième partie de la thèse concerne la formation de particules à base de chitosane. La méthode choisie consiste à complexer le chitosane avec un polye lectrolyte naturel de charge opposée, le sulfate de dextrane. De nombreux paramètres liés à la réaction de complexation ont été étudiés et finalement un procédé simple et efficace, permettant l'obtention de particules chargées positivement ou négativement, a été développéLYON1-BU.Sciences (692662101) / SudocSudocFranceF
Structure, thermodynamic and kinetic signatures of a synthetic polyelectrolyte coacervating system
While many studies on coacervation have targeted biomacromolecules, we review in this article the key structure, thermodynamic and kinetic features of a fully synthetic coacervating system based on polyacrylic acid (PAA) and poly(diallyldimethylammonium chloride) (PDADMAC) oppositely charged polyelectrolytes at pH 10, where PAA chains are fully deprotonated. Among the main points of interest, we can highlight (i) the presence of polyelectrolyte complex (PEC) nanoparticles that, unexpectedly, coexist with a certain amount of coacervate droplets in a large range of compositions, even far from stoichiometry; (ii) the fact that these PEC nanoparticles are likely precursors of the coacervation occurring at stoichiometry; (iii) the formation of soluble PECs only in a certain range of physicochemical conditions; (iv) the equilibrium properties of the system; (v) and last but not least a distinctive kinetic signature at stoichiometry evidenced by a peak in light scattering at very short times (~ 100 ms). Some of these results can be rationalized on the basis of weak interaction unfolding between oppositely charged PAA and PDADMAC chains as revealed by microcalorimetry measurements.Assemblage Macromoléculaire Hors-équilibre Compréhension, Contrôle & nouvelles structure
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