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ACS Chemical Biology Mar 2022Heparin products are widely used clinical anticoagulants essential in the practice of modern medicine. Low-molecular-weight heparins (LMWHs) are currently prepared by...
Heparin products are widely used clinical anticoagulants essential in the practice of modern medicine. Low-molecular-weight heparins (LMWHs) are currently prepared by the controlled chemical or enzymatic depolymerization of unfractionated heparins (UFHs) that are extracted from animal tissues. In many clinical applications, LMWHs have displaced UFHs and currently comprise over 60% of the heparin market. In the past, our laboratory has made extensive efforts to prepare bioengineered UFHs relying on a chemoenzymatic process to address concerns about animal-sourced UFHs. The current study describes the use of a novel chemoenzymatic process to prepare a chemobiosynthetic LMWH from a low-molecular-weight heparosan. The resulting chemobiocatalytic LMWH matches most of the United States pharmacopeial specifications for enoxaparin, a LMWH prepared through the base-catalyzed depolymerization of animal-derived UFH.
Topics: Animals; Anticoagulants; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Molecular Weight
PubMed: 35201757
DOI: 10.1021/acschembio.1c00928 -
Communications Biology Sep 2023Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on... (Review)
Review
Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on surface-attached formations, but detached aggregates have received increasing attention in the past decade due to their pivotal role in chronic infections. Understanding their nature sparked fervent discussions in biofilm conferences and scientific literature. This review consolidates current insights on non-attached aggregates, offering examples of their occurrence in nature and diseases. We discuss their formation and dispersion mechanisms, resilience to antibiotics and immune-responses, drawing parallels to surface-attached biofilms. Moreover, we outline available in vitro models for studying non-attached aggregates.
Topics: Anti-Bacterial Agents; Biofilms; Molecular Weight
PubMed: 37658117
DOI: 10.1038/s42003-023-05281-4 -
Biopolymers Sep 2021Chitooligosaccharides (COS) differ from chitosan by their molar mass: those of COS are defined to be lower than 20 kg mol . Their functionalization is widely... (Review)
Review
Chitooligosaccharides (COS) differ from chitosan by their molar mass: those of COS are defined to be lower than 20 kg mol . Their functionalization is widely described in the literature and leads to the introduction of new properties that broaden their application fields. Like chitosan, COS modification sites are mainly primary amine and hydroxyl groups. Among their chemical modification, one can find amidation or esterification, epoxy-amine/hydroxyl coupling, Schiff base formation, and Michael addition. When depolymerized through nitrous deamination, COS bear an aldehyde at the chain end that can open the way to other chemical reactions and lead to the synthesis of new interesting amphiphilic structures. This article details the recent developments in COS functionalization, primarily focusing on amine and hydroxyl groups and aldehyde-chain end reactions, as well as paying considerable attention to other types of modification. We also describe and compare the different functionalization protocols found in the literature while highlighting potential mistakes made in the chemical structures accompanied with suggestions. Such chemical modification can lead to new materials that are generally nontoxic, biobased, biodegradable, and usable in various applications.
Topics: Chitin; Chitosan; Molecular Weight; Oligosaccharides
PubMed: 34115397
DOI: 10.1002/bip.23461 -
Topics in Current Chemistry (Cham) Aug 2022Glycopolymer materials have emerged as a significant biopolymer class that has piqued the scientific community's attention due to their potential applications. Recently,... (Review)
Review
Glycopolymer materials have emerged as a significant biopolymer class that has piqued the scientific community's attention due to their potential applications. Recently, they have been found to be a unique synthetic biomaterial; glycopolymer materials have also been used for various applications, including direct therapeutic methods, medical adhesives, drug/gene delivery systems, and biosensor applications. Therefore, for the next stage of biomaterial research, it is essential to understand current breakthroughs in glycopolymer-based materials research. This review discusses the most widely utilized synthetic methodologies for glycopolymer-based materials, their properties based on structure-function interactions, and the significance of these materials in biosensing applications, among other topics. When creating glycopolymer materials, contemporary polymerization methods allow precise control over molecular weight, molecular weight distribution, chemical activity, and polymer architecture. This review concludes with a discussion of the challenges and complexities of glycopolymer-based biosensors, in addition to their potential applications in the future.
Topics: Biocompatible Materials; Biosensing Techniques; Molecular Weight; Polymerization; Polymers
PubMed: 35951265
DOI: 10.1007/s41061-022-00395-5 -
International Journal of Molecular... Aug 2022(Berk.) Pegler, also known as shiitake mushroom, is a popular edible macrofungus and a source of numerous bioactive substances with multiple beneficial health effects.... (Review)
Review
(Berk.) Pegler, also known as shiitake mushroom, is a popular edible macrofungus and a source of numerous bioactive substances with multiple beneficial health effects. -derived polysaccharides are the most valuable compounds, with anticancer, antioxidant, antimicrobial, and immunomodulatory properties. It has been demonstrated that their biological activity depends on the extraction method, which affects monosaccharide composition, molecular weight, branching degrees, and helical conformation. In this review, we discuss the immunomodulatory properties of various polysaccharides from in animal models and in humans.
Topics: Animals; Antineoplastic Agents; Antioxidants; Humans; Molecular Weight; Polysaccharides; Shiitake Mushrooms
PubMed: 36012249
DOI: 10.3390/ijms23168980 -
Molecular Diversity May 2021Respiratory sensitization has been considered an important toxicological endpoint, because of the severe risk to human health. A great part of sensitization events were...
Respiratory sensitization has been considered an important toxicological endpoint, because of the severe risk to human health. A great part of sensitization events were caused by low molecular weight (< 1000) respiratory sensitizers in the past decades. However, there is currently no widely accepted test method that can identify prospective low molecular weight respiratory sensitisers. Herein, we performed the study of modeling and insights into molecular basis of low molecular weight respiratory sensitizers with a high-quality data set containing 136 respiratory sensitizers and 518 nonsensitizers. We built a number of classification models by using OCHEM tools, and a consensus model was developed based on the ten best individual models. The consensus model showed good predictive ability with a balanced accuracy of 0.78 and 0.85 on fivefold cross-validation and external validation, respectively. The readers can predict the respiratory sensitization of organic compounds via https://ochem.eu/article/114857 . The effect of several molecular properties on respiratory sensitization was also evaluated. The results indicated that these properties differ significantly between respiratory sensitizers and nonsensitizers. Furthermore, 14 privileged substructures responsible for respiratory sensitization were identified. We hope the models and the findings could provide useful help for environmental risk assessment.
Topics: Allergens; Machine Learning; Models, Molecular; Molecular Weight; Respiratory Hypersensitivity
PubMed: 32166484
DOI: 10.1007/s11030-020-10069-3 -
Biomedical Materials (Bristol, England) Sep 2022Hyaluronic acid (HA) hydrogels have been used for a multitude of applications, perhaps most notably for tissue engineering and regenerative medicine, owing to the...
Hyaluronic acid (HA) hydrogels have been used for a multitude of applications, perhaps most notably for tissue engineering and regenerative medicine, owing to the versatility of the polymer and its tunable nature. Various groups have investigated the impact of hydrogel parameters (e.g. molecular weight, concentration, stiffness, etc)andto achieve desired material performance characteristics. A limitation in the literature to date has been that altering one hydrogel parameter (a 'manipulated variable') to achieve a given hydrogel characteristic (a 'controlled variable') changes two variables at a time (e.g. altering molecular weight and/or concentration to investigate cell response to stiffness). Therefore, if cell responses differ, it may be possible that more than one variable caused the changes in observed responses. In the current study, we leveraged thiol-ene click chemistry with a crosslinker to develop a method that minimizes material performance changes and permitted multiple material properties to be independently held constant to evaluate a single variable at a time. Independent control was accomplished by tuning the concentration of crosslinker to achieve an effectively constant stiffness for different HA hydrogel molecular weights and polymer concentrations. Specific formulations were thereby identified that enabled the molecular weight (76-1550 kDa), concentration (2%-10%), or stiffness (∼1-350 kPa) to be varied while the other two were held constant, a key technical achievement. The response of rat mesenchymal stem cells to varying molecular weight, concentration, and stiffness demonstrated consistent upregulation of osteocalcin gene expression. The methodology presented to achieve independent control of hydrogel parameters may potentially be adopted by others for alternative hydrogel polymers, cell types, or cell culture medium compositions to minimize confounding variables in experimental hydrogel designs.
Topics: Animals; Chondrogenesis; Hyaluronic Acid; Hydrogels; Molecular Weight; Polymers; Rats
PubMed: 36044886
DOI: 10.1088/1748-605X/ac8e41 -
Journal of the American Chemical Society Dec 2022Control of polymer molecular weight is critical for tailoring structure-function properties; however, traditional molecular weight characterization techniques have...
Control of polymer molecular weight is critical for tailoring structure-function properties; however, traditional molecular weight characterization techniques have limited ability to determine the molecular weight of polymers in real time without sample removal from the reaction mixture, with spatial resolution, and of insoluble polymers. In this work, a fluorescence lifetime imaging microscopy (FLIM) method was developed that overcomes these limitations. The method is demonstrated with polynorbornene and polydicyclopentadiene, polymers derived from ruthenium-catalyzed ring-opening metathesis polymerization (ROMP). The polymer , ranging from 35 to 570 kg/mol as determined by gel-permeation chromatography, was quantitatively correlated with the fluorescence lifetime. The revealed correlation then enabled time-resolved measurement of during an ongoing ROMP reaction, requiring only 1 s per measurement (of a 45 μm × 45 μm polymer sample area), and provided spatial resolution, resulting in simultaneous characterization of polymer morphology. To provide the fluorescence signal, the initial reaction solutions contained a very low doping of a reactive norbornene monomer labeled with fluorescent boron dipyrromethene (BODIPY), such that 1 in every 10 monomers contained a fluorophore. The resulting FLIM visualization method enables the rapid determination of the molecular weights of growing polymers without removal from the reaction mixture and regardless of polymer solubility.
Topics: Molecular Weight; Polymers; Polymerization; Ruthenium; Chromatography, Gel
PubMed: 36459633
DOI: 10.1021/jacs.2c10036 -
Analytical Chemistry Nov 2022Hydrodynamic chromatography (HDC) is a well-established analytical separation method for the size separation of nano- and microparticles and large molecular weight...
Hydrodynamic chromatography (HDC) is a well-established analytical separation method for the size separation of nano- and microparticles and large molecular weight solutes such as synthetic polymers and proteins. We report on a theoretical study showing that the separation resolution of open-tubular HDC can be significantly enhanced by changing the cross-sectional shape of the separation channel. By enforcing Brenner's macro-transport approach, we provide theoretical/numerical evidence showing how the shape of the cross section influences quantitatively both the selectivity and the axial dispersion of the suspended particles in HDC. The separation performance of square-, triangle-, and star-shaped channel cross sections is compared to that of a cylindrical capillary over three decades of the particle Péclet number in terms of the minimal separation length and time to obtain the unit resolution of a two-particle mixture. Enhancement factors up to 400% are found in the case of triangular shapes, with the best performing case being the 70.6° angle, which can be obtained by KOH etching of bulk silicon.
Topics: Hydrodynamics; Particle Size; Chromatography; Polymers; Molecular Weight
PubMed: 36370088
DOI: 10.1021/acs.analchem.2c02766 -
PloS One 2021Rapid advancements in long-read sequencing technologies have transformed read lengths from bps to Mbps, which has enabled chromosome-scale genome assemblies. However,...
Rapid advancements in long-read sequencing technologies have transformed read lengths from bps to Mbps, which has enabled chromosome-scale genome assemblies. However, read lengths are now becoming limited by the extraction of pure high-molecular weight DNA suitable for long-read sequencing, which is particularly challenging in plants and fungi. To overcome this, we present a protocol collection; high-molecular weight DNA extraction, clean-up and size selection for long-read sequencing. We optimised a gentle magnetic bead based high-molecular weight DNA extraction, which is presented here in detail. The protocol circumvents spin columns and high-centrifugation, to limit DNA fragmentation. The protocol is scalable based on tissue input, which can be used on many species of plants, fungi, reptiles and bacteria. It is also cost effective compared to kit-based protocols and hence applicable at scale in low resource settings. An optional sorbitol wash is listed and is highly recommended for plant and fungal tissues. To further remove any remaining contaminants such as phenols and polysaccharides, optional DNA clean-up and size selection strategies are given. This protocol collection is suitable for all common long-read sequencing platforms, such as technologies offered by PacBio and Oxford Nanopore. Using these protocols, sequencing on the Oxford Nanopore MinION can achieve read length N50 values of 30-50 kb, with reads exceeding 200 kb and outputs ranging from 15-30 Gbp. This has been routinely achieved with various plant, fungi, animal and bacteria samples.
Topics: DNA; High-Throughput Nucleotide Sequencing; Molecular Weight; Nanopores; Sequence Analysis, DNA
PubMed: 34264958
DOI: 10.1371/journal.pone.0253830