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The Journal of Biological Chemistry Jun 2019Tubulin, the subunit of microtubules, is a noncovalent heterodimer composed of one α- and one β-tubulin monomer. Both tubulins are encoded by multiple genes or...
Tubulin, the subunit of microtubules, is a noncovalent heterodimer composed of one α- and one β-tubulin monomer. Both tubulins are encoded by multiple genes or composed of different isotypes, which are differentially expressed in different tissues and in development. Tubulin αβ dimers are found throughout the eukaryotes and, although very similar, are known to differ among organisms. We seek to investigate tubulins from different tissues and different organisms for a basic physical characteristic: heterodimer stability and monomer exchange between heterodimers. We previously showed that mammalian brain tubulin heterodimers reversibly dissociate, following the mass action law. Dissociation yields native monomers that can exchange with added tubulin to form new heterodimers. Here, we compared the dissociation of tubulins from multiple sources, including mammalian (rat) brain, cultured human cells (HeLa cells), chicken brain, chicken erythrocytes, and the protozoan We used fluorescence-detected analytical ultracentrifugation to measure tubulin dissociation over a >1000-fold range in concentration and found that tubulin heterodimers from different biological sources differ in by as much as 150-fold under the same conditions. Furthermore, when fluorescent tracer tubulins from various sources were titrated with unlabeled tubulin from a single source (rat brain tubulin), heterologous dimerization occurred, exhibiting similar affinities, in some cases binding even more strongly than with autologous tubulin. These results provide additional insight into the regulation of heterodimer formation of tubulin from different biological sources, revealing that monomer exchange appears to contribute to the sorting of α- and β-tubulin monomers that associate following tubulin folding.
Topics: Amino Acid Sequence; Animals; Brain; Chickens; Erythrocytes; Humans; Leishmania; Models, Molecular; Protein Conformation; Protein Multimerization; Rats; Sequence Homology; Tubulin
PubMed: 31110044
DOI: 10.1074/jbc.RA119.007973 -
Molecules (Basel, Switzerland) Feb 2023Galectin-10 (Gal-10) forms Charcot-Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a...
Galectin-10 (Gal-10) forms Charcot-Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer-dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases.
Topics: Humans; Lactose; Galactose; Crystallization; Galectins; Binding Sites
PubMed: 36838965
DOI: 10.3390/molecules28041979 -
Biomedicine & Pharmacotherapy =... Jan 2023Cervical cancer (CC), as the most common malignant tumor of the female reproductive system, is infamous for its high morbidity and mortality rates. Its development and... (Review)
Review
Cervical cancer (CC), as the most common malignant tumor of the female reproductive system, is infamous for its high morbidity and mortality rates. Its development and metastasis are intricate because numerous signaling pathways are involved. Since the cancer and the PI3K/Akt signaling pathway are closely intertwined, direct inhibition of either the PI3K/Akt pathway or its target genes and molecules may be remarkably constructive for treatment. Albeit remarkable advances in the treatment of CC, existing common anti-cancer medications are not without problems. These problems include myelotoxicity, cardiotoxicity, genotoxicity, and vasospasm, which are the most common and well-recognized toxicities associated with these medications. Therefore, it is necessary and urgent to develop novel, potent, secure, and more reasonably priced anticancer medications that are void of the above problems. Against this backdrop, Chinese medicine monomers have received more attention in recent years owing to their safety, low toxicity, few side effects, and anti-tumor properties. By regulating the PI3K/Akt signaling pathway, Chinese medicine monomers are effective not only in inhibiting CC growth, proliferation, apoptosis, invasion, migration, and reversing drug resistance but also in a variety of targets. Most previous earlier studies focused on the use of a single traditional Chinese medicine monomer to treat CC by regulating the PI3K/Akt signaling pathway rather than a combination of several such monomers. More importantly, to our knowledge, there has hardly been any study providing an exhaustive and comprehensive review of all the Chinese medicine monomers at CC. In response to this scarcity, we attempt in this paper to provide a comprehensive review of all the literature to date on traditional Chinese medicine monomers at cervical cancer, highlight the mechanisms and future prospects for their use in the prevention and treatment of cervical cancer.
Topics: Female; Humans; Apoptosis; Cell Line, Tumor; Cell Proliferation; Medicine, Chinese Traditional; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Uterine Cervical Neoplasms
PubMed: 36481407
DOI: 10.1016/j.biopha.2022.114084 -
Angewandte Chemie (International Ed. in... May 2021Aldehyde groups enable facile conjugation to proteins, enzymes, oligonucleotides or fluorescent dyes, yet there are no literature examples of water-soluble...
Aldehyde groups enable facile conjugation to proteins, enzymes, oligonucleotides or fluorescent dyes, yet there are no literature examples of water-soluble aldehyde-functional vinyl monomers. We report the synthesis of a new hydrophilic cis-diol-based methacrylic monomer (GEO5MA) by transesterification of isopropylideneglycerol penta(ethylene glycol) using methyl methacrylate followed by acetone deprotection via acid hydrolysis. The corresponding water-soluble aldehyde monomer, AGEO5MA, is prepared by aqueous periodate oxidation of GEO5MA at 22 °C. RAFT polymerization of GEO5MA yields the water-soluble homopolymer, PGEO5MA. Aqueous periodate oxidation of the terminal cis-diol units on PGEO5MA at 22 °C affords a water-soluble aldehyde-functional homopolymer (PAGEO5MA). Moreover, a library of hydrophilic statistical copolymers bearing cis-diol and aldehyde groups was prepared using sub-stoichiometric periodate/cis-diol molar ratios. The aldehyde groups on PAGEO5MA homopolymer were reacted in turn with three amino acids to demonstrate synthetic utility.
PubMed: 33617018
DOI: 10.1002/anie.202015298 -
Molecules (Basel, Switzerland) Oct 2021The increase of the global population and shortage of renewable water resources urges the development of possible remedies to improve the quality and reusability of... (Review)
Review
The increase of the global population and shortage of renewable water resources urges the development of possible remedies to improve the quality and reusability of waste and contaminated water supplies. Different water pollutants, such as heavy metals, dyes, pesticides, endocrine disrupting compounds (EDCs), and pharmaceuticals, are produced through continuous technical and industrial developments that are emerging with the increasing population. Molecularly imprinted polymers (MIPs) represent a class of synthetic receptors that can be produced from different types of polymerization reactions between a target template and functional monomer(s), having functional groups specifically interacting with the template; such interactions can be tailored according to the purpose of designing the polymer and based on the nature of the target compounds. The removal of the template using suitable knocking out agents renders a recognition cavity that can specifically rebind to the target template which is the main mechanism of the applicability of MIPs in electrochemical sensors and as solid phase extraction sorbents. MIPs have unique properties in terms of stability, selectivity, and resistance to acids and bases besides being of low cost and simple to prepare; thus, they are excellent materials to be used for water analysis. The current review represents the different applications of MIPs in the past five years for the detection of different classes of water and wastewater contaminants and possible approaches for future applications.
PubMed: 34770924
DOI: 10.3390/molecules26216515 -
Journal of Leukocyte Biology Feb 2012Chemokines exert their function by binding the GPCR class of receptors on leukocytes and cell surface GAGs in target tissues. Most chemokines reversibly exist as... (Comparative Study)
Comparative Study
Chemokines exert their function by binding the GPCR class of receptors on leukocytes and cell surface GAGs in target tissues. Most chemokines reversibly exist as monomers and dimers, but very little is known regarding the molecular mechanisms by which the monomer-dimer equilibrium modulates in vivo function. For the chemokine CXCL8, we recently showed in a mouse lung model that monomers and dimers are active and that the monomer-dimer equilibrium of the WT plays a crucial role in regulating neutrophil recruitment. In this study, we show that monomers and dimers are also active in the mouse peritoneum but that the role of monomer-dimer equilibrium is distinctly different between these tissues and that mutations in GAG-binding residues render CXCL8 less active in the peritoneum but more active in the lung. We propose that tissue-specific differences in chemokine gradient formation, resulting from tissue-specific differences in GAG interactions, are responsible for the observed differences in neutrophil recruitment. Our observation of differential roles played by the CXCL8 monomer-dimer equilibrium and GAG interactions in different tissues is novel and reveals an additional level of complexity of how chemokine dimerization regulates in vivo recruitment.
Topics: Amino Acid Substitution; Animals; Chemotaxis, Leukocyte; Dimerization; Female; Glycosaminoglycans; Humans; Interleukin-8; Lung; Mice; Mice, Inbred BALB C; Models, Molecular; Mutagenesis, Site-Directed; Neutrophils; Organ Specificity; Peritoneum; Protein Binding; Protein Conformation; Recombinant Fusion Proteins; Specific Pathogen-Free Organisms
PubMed: 22140266
DOI: 10.1189/jlb.0511239 -
Polymers May 2021More environmentally friendly polymeric materials for use in corrosive conditions were obtained in the process of UV polymerization of terpene methacrylate monomers:...
More environmentally friendly polymeric materials for use in corrosive conditions were obtained in the process of UV polymerization of terpene methacrylate monomers: geranyl methacrylate and citronellyl methacrylate and the commercially available monomer methyl methacrylate. Selected properties (solvent resistance, chemical resistance, glass transition temperature, thermal stability, and decomposition course during heating) were evaluated. It was found that the properties of the materials directly depended on the monomer percentage and the conditioning temperatures used. An increase in the geranyl or citronellyl methacrylate monomer content in the copolymers reduced the solubility and chemical resistance of the materials post-cured at 50 °C. The samples post-cured at 120 °C were characterized by high resistance to polar and non-polar solvents and the chemical environment, regardless of the percentage composition. The glass transition temperatures for samples conditioned at 120 °C increased with increasing content of methyl methacrylate in the copolymers. The thermal stability of copolymers depended on the conditioning temperatures used. It was greater than 200 °C for most copolymers post-cured at 120 °C. The process of pyrolysis of copolymers led to the emission of geranyl methacrylate, citronellyl methacrylate, and methyl methacrylate monomers as the main pyrolysis volatiles.
PubMed: 34065176
DOI: 10.3390/polym13101659 -
Polymers Jan 2024Through the graft polymerization of acrylic monomers onto starch, materials with interesting new properties can be synthesized. Fenton's chemistry, Fe/HO, is considered... (Review)
Review
Through the graft polymerization of acrylic monomers onto starch, materials with interesting new properties can be synthesized. Fenton's chemistry, Fe/HO, is considered to be attractive for the initiation of graft polymerization with the monomer acrylic acid since it is cheap and reacts quickly at ambient conditions and should therefore be easy to scale up. However, the selectivity of the grafting versus the homopolymerization reaction poses a challenge with this monomer and this type of initiator. In the present review paper, we investigate why data from the literature on grafting systems with other monomers and initiation systems tend to show higher graft selectivity. A scheme is presented, based on reaction engineering principles, that supports an explanation for these observed differences. It is found that more selective activation of starch is a factor, but perhaps even more important is a low monomer-to-starch ratio at the starting sites of graft reactions. Since water is the most common solvent, monomers that are less water-soluble have an advantage in this respect. Based on the proposed scheme, methods to improve the graft selectivity with Fenton's initiator and acrylic acid are evaluated. Most promising appears to be a method of gradual monomer dosage. With gelatinized cassava starch in a batch reactor, both the grafting percentage (17 => 29%) and graft selectivity (18 => 31%) could be improved. This can be considered a principal breakthrough. Still, more research and development would be needed to refine the method and to implement the idea in a continuous reactor at a larger scale.
PubMed: 38257054
DOI: 10.3390/polym16020255 -
ACS Omega Mar 2024Six poly(amic acid)s (PAAs) were synthesized by reacting bis(3-aminophenyl) sulfone with various dianhydride monomers such as pyromellitic dianhydride, 4,4'-biphthalic...
Six poly(amic acid)s (PAAs) were synthesized by reacting bis(3-aminophenyl) sulfone with various dianhydride monomers such as pyromellitic dianhydride, 4,4'-biphthalic anhydride, dicyclohexyl-3,4,3',4'-tetracarboxylic dianhydride, 4,4'-oxidiphthalic anhydride, 3,3',4,4'-benzophenonetetracarboxylic dianhydride, and 4,4'-(hexafluoroisopropylidene) diphthalic anhydride. These PAAs were then converted to polyimide (PI) films by thermal imidization at various temperatures. To obtain colorless and transparent PI (CPI), the dianhydride monomer used in this study had an overall bent structure, a structure containing a strong electron-withdrawing -CF substituent or an alicyclic ring. In addition, some monomers contained ether or ketone functional groups in their bent structures. The thermomechanical properties, optical transparency, and solubility of CPI films with six different dianhydride monomer structures were investigated, and the correlation between the monomer structure and CPI film properties was clarified. Overall, CPI with an aromatic main chain structure or a linear structure had excellent thermal and mechanical properties. In contrast, CPI with a bent structure containing functional groups or substituents in the main chain exhibited excellent optical transparency and solubility.
PubMed: 38497003
DOI: 10.1021/acsomega.4c00175 -
Polymers May 2023To address the increasing demand for biobased materials, lignin-derived ferulic acid (FA) is a promising candidate. In this study, an FA-derived styrene-like monomer,...
To address the increasing demand for biobased materials, lignin-derived ferulic acid (FA) is a promising candidate. In this study, an FA-derived styrene-like monomer, referred to as 2-methoxy-4-vinylphenol (MVP), was used as the platform to prepare functional monomers for radical polymerizations. Hydrophobic biobased monomers derived from MVP were polymerized via solution and emulsion polymerization resulting in homo- and copolymers with a wide range of thermal properties, thus showcasing their potential in thermoplastic applications. Moreover, divinylbenzene (DVB)-like monomers were prepared from MVP by varying the aliphatic chain length between the MVP units. These biobased monomers were thermally crosslinked with thiol-bearing reagents to produce thermosets with different crosslinking densities in order to demonstrate their thermosetting applications. The results of this study expand the scope of MVP-derived monomers that can be used in free-radical polymerizations toward the preparation of new biobased and functional materials from lignin.
PubMed: 37177314
DOI: 10.3390/polym15092168