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Marine Drugs Jul 2023Microalgae are abundant components of the biosphere rich in low molecular weight carbohydrate-containing natural products (glycoconjugates). Glycoconjugates take part in... (Review)
Review
Microalgae are abundant components of the biosphere rich in low molecular weight carbohydrate-containing natural products (glycoconjugates). Glycoconjugates take part in the processes of photosynthesis, provide producers with important biological molecules, influence other organisms and are known by their biological activities. Some of them, for example, glycosylated toxins and arsenicals, are detrimental and can be transferred via food chains into higher organisms, including humans. So far, the studies on a series of particular groups of microalgal glycoconjugates were not comprehensively discussed in special reviews. In this review, a special focus is given to glycoconjugates' isolation, structure determination, properties and approaches to search for new bioactive metabolites. Analysis of literature data concerning structures, functions and biological activities of ribosylated arsenicals, galactosylated and sulfoquinovosylated lipids, phosphoglycolipids, glycoside derivatives of toxins, and other groups of glycoconjugates was carried out and discussed. Recent studies were fundamental in the discovery of a great variety of new carbohydrate-containing metabolites and their biological activities in defining the role of microalgal viral infections in regulating microalgal blooms as well as in the detection of glycoconjugates with potent immunomodulatory properties. Those discoveries support growing interest in these molecules.
Topics: Humans; Microalgae; Molecular Weight; Glycosides; Photosynthesis; Arsenicals
PubMed: 37623708
DOI: 10.3390/md21080427 -
Frontiers in Immunology 2022
Topics: Humans; Immune Checkpoint Inhibitors; Immunotherapy; Molecular Weight; Neoplasms
PubMed: 35663988
DOI: 10.3389/fimmu.2022.920442 -
Carbohydrate Research Nov 2019Fucoidan is a unique polysaccharide that has various biological activities partly owing to its capability to act as mimetics of natural ligands of protein receptors.... (Review)
Review
Fucoidan is a unique polysaccharide that has various biological activities partly owing to its capability to act as mimetics of natural ligands of protein receptors. However, its use is limited due to a number of reasons including those associated with molecular weight and composition variation in relation to an algae type and habitat, raw material collection time, extraction method and duration. The main problem which limits its application in therapy is high molecular weight and seasonal composition. To expand the scope of its application, it is necessary to develop a validated procedure of high-molecular-weight fucoidan depolymerization or synthesis of its oligomeric elements . Therefore, there is a need for the synthesis of polysaccharideoligomeric components and/or polymer mimetics which allow for the creation of chains with a certain degree of sulfation, molecular weight and yield. This paper presents the most commonly used methods of fucoidan homopolysaccharide and heteropolysaccharide fragments synthesis as well as problems associated with their synthesis, including fucoidan analogues available in the form of glycopolymers that are obtained by using different methods of radical polymerization. These fucoidan mimetic glycopolymers have a biological activity similar to that of native fucoidans with high yield, which allows for their use as potential agents in the pharmaceutical industry.
Topics: Chemistry Techniques, Synthetic; Molecular Weight; Polymerization; Polysaccharides
PubMed: 31526929
DOI: 10.1016/j.carres.2019.107806 -
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 -
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 -
Journal of Medicinal Chemistry Dec 2018Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal... (Review)
Review
Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescribed medications, as well as provide case studies on recently approved lead-like drugs. Many of these recent drugs are close analogs of previously known drugs or natural substrates, with a key focus of their medicinal chemistry optimization being the choice of a low molecular weight starting point and maintaining low molecular weight during the optimization. However, the identification of low molecular weight starting points may be limited by the availability of suitable low molecular weight screening sets. To increase the discovery rate of lead-like drugs, we suggest an increased focus on inclusion and prosecution of lead-like starting points in screening libraries.
Topics: Drug Discovery; Drug Evaluation, Preclinical; Molecular Weight
PubMed: 30052440
DOI: 10.1021/acs.jmedchem.8b00407 -
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 -
International Journal of Molecular... Mar 2023High molecular weight (MW), highly repetitive protein polymers are attractive candidates to replace petroleum-derived materials as these protein-based materials (PBMs)... (Review)
Review
High molecular weight (MW), highly repetitive protein polymers are attractive candidates to replace petroleum-derived materials as these protein-based materials (PBMs) are renewable, biodegradable, and have outstanding mechanical properties. However, their high MW and highly repetitive sequence features make them difficult to synthesize in fast-growing microbial cells in sufficient amounts for real applications. To overcome this challenge, various methods were developed to synthesize repetitive PBMs. Here, we review recent strategies in the construction of repetitive genes, expression of repetitive proteins from circular mRNAs, and synthesis of repetitive proteins by ligation and protein polymerization. We discuss the advantages and limitations of each method and highlight future directions that will lead to scalable production of highly repetitive PBMs for a wide range of applications.
Topics: Polymers; Molecular Weight; Proteins; Repetitive Sequences, Nucleic Acid
PubMed: 37047388
DOI: 10.3390/ijms24076416