A study of Ca(2+)-heparin complex-formation by polarimetry.
Ontology highlight
ABSTRACT:
SUBMITTER: Grant D
PROVIDER: S-EPMC1130824 | biostudies-other | 1992 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Plots analogous to isothermal binding curves were derived from polarimetric studies of solutions of Na(+)-heparin to which Cu2+ was added. The shape of the plots suggests that discrete Cu(2+)-heparin complexes may form, the nature and stoichiometry of which depend upon the conditions under which the interaction occurs. Initially, complexes were formed with a stoichiometry of about 1 Cu2+ ion per heparin tetrasaccharide unit. Under these conditions, the complex may exist as a colloid-like phase that is not subject to simple solution equilibrium processes, and that is maintained by forces in addition to electrostatic ones. Further addition of Cu2+ resulted in the formation of a different complex with a stoichiometry of about 1 Cu2+ ion per disaccharide unit.
| S-EPMC1131020 | biostudies-other
Project description:Recent studies have shown that ultra-large complexes (ULCs) of platelet factor 4 (PF4) and heparin (H) play an essential role in the pathogenesis of heparin-induced thrombocytopenia (HIT), an immune-mediated disorder caused by PF4/H antibodies. Because antigenic PF4/H ULCs assemble through non-specific electrostatic interactions, we reasoned that disruption of charge-based interactions can modulate the immune response to antigen. We tested a minimally anticoagulant compound (2-O, 3-O desulfated heparin, ODSH) with preserved charge to disrupt PF4/H complex formation and immunogenicity. We show that ODSH disrupts complexes when added to pre-formed PF4/H ULCs and prevents ULC formation when incubated simultaneously with PF4 and UFH. In other studies, we show that excess ODSH reduces HIT antibody (Ab) binding in immunoassays and that PF4/ODSH complexes do not cross-react with HIT Abs. When ODSH and unfractionated heparin (UFH) are mixed at equimolar concentrations, we show that there is a negligible effect on amount of protamine required for heparin neutralisation and reduced immunogenicity of PF4/UFH in the presence of ODSH. Taken together, these studies suggest that ODSH can be used concurrently with UFH to disrupt PF4/H charge interactions and provides a novel strategy to reduce antibody mediated complications in HIT.
| S-EPMC4441624 | biostudies-literature
Project description:Chemicals such as anionic surfactants and polymers often contain groups that complex divalent ions such as Ca2+. The formation of divalent ion complexes can decrease emulsifying or viscosifying power and lead to adsorption or precipitation. This is particularly relevant in chemical enhanced oil recovery, where high viscosities and low interfacial tensions are required for mobility control and the formation of oil-water microemulsions, respectively. In this work, we use a Ca2+-sensitive dye to determine the Ca2+ concentration and Ca-complex formation constants in solutions containing complexing agents. This method can be used to rapidly screen the affinity of different chemicals to form Ca-complexes in low-salinity solutions. The complex formation constants can be implemented into chemical flooding simulators to investigate the interplay with mineral dissolution and cation exchange and model adsorption processes.
| S-EPMC7905941 | biostudies-literature
Project description:Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequence-based search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.
| S-EPMC4038792 | biostudies-literature
Project description:Photosynthetic O2 evolution is catalyzed by the Mn4CaO5 cluster of the water oxidation complex of the photosystem II (PSII) complex. The photooxidative self-assembly of the Mn4CaO5 cluster, termed photoactivation, utilizes the same highly oxidizing species that drive the water oxidation in order to drive the incorporation of Mn2+ into the high-valence Mn4CaO5 cluster. This multistep process proceeds with low quantum efficiency, involves a molecular rearrangement between light-activated steps, and is prone to photoinactivation and misassembly. A sensitive polarographic technique was used to track the assembly process under flash illumination as a function of the constituent Mn2+ and Ca2+ ions in genetically engineered membranes of the cyanobacterium Synechocystis sp. PCC6803 to elucidate the action of Ca2+ and peripheral proteins. We show that the protein scaffolding organizing this process is allosterically modulated by the assembly protein Psb27, which together with Ca2+ stabilizes the intermediates of photoactivation, a feature especially evident at long intervals between photoactivating flashes. The results indicate three critical metal-binding sites: two Mn and one Ca, with occupation of the Ca site by Ca2+ critical for the suppression of photoinactivation. The long-observed competition between Mn2+ and Ca2+ occurs at the second Mn site, and its occupation by competing Ca2+ slows the rearrangement. The relatively low overall quantum efficiency of photoactivation is explained by the requirement of correct occupancy of these metal-binding sites coupled to a slow restructuring of the protein ligation environment, which are jointly necessary for the photooxidative trapping of the first stable assembly intermediate.
| S-EPMC7668025 | biostudies-literature
Project description:Surface plasmon resonators can drastically redistribute incident light over different output wave vectors and polarizations. This can lead for instance to sub-diffraction sized nanoapertures in metal films that beam and to nanoparticle antennas that enable efficient conversion of photons between spatial modes, or helicity channels. We present a polarimetric Fourier microscope as a new experimental tool to completely characterize the angle-dependent polarization-resolved scattering of single nanostructures. Polarimetry allows determining the full Stokes parameters from just six Fourier images. The degree of polarization and the polarization ellipse are measured for each scattering direction collected by a high NA objective. We showcase the method on plasmonic bullseye antennas in a metal film, which are known to beam light efficiently. We find rich results for the polarization state of the beamed light, including complete conversion of input polarization from linear to circular and from one helicity to another. In addition to uncovering new physics for plasmonic groove antennas, the described technique projects to have a large impact in nanophotonics, in particular towards the investigation of a broad range of phenomena ranging from photon spin Hall effects, polarization to orbital angular momentum transfer and design of plasmon antennas.
| S-EPMC4415650 | biostudies-literature
Project description:The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine and threonine residues on proteins is referred to as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) is the enzyme responsible for carrying out the modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has been implicated in a wide range of cellular processes including transcription, proteostasis, and stress response. Dysregulation of O-GlcNAc has been linked to diabetes, cancer, and neurodegenerative and cardiovascular disease. OGA has been proposed to be a drug target for the treatment of Alzheimer's and cardiovascular disease given that increased O-GlcNAc levels appear to exert a protective effect. The search for specific, potent, and drug-like OGA inhibitors with bioavailability in the brain is therefore a field of active research, requiring orthogonal high-throughput assay platforms. Here, we describe the synthesis of a novel probe for use in a fluorescence polarization based assay for the discovery of inhibitors of OGA. We show that the probe is suitable for use with both human OGA, as well as the orthologous bacterial counterpart from Clostridium perfringens, CpOGA, and the lysosomal hexosaminidases HexA/B. We structurally characterize CpOGA in complex with a ligand identified from a fragment library screen using this assay. The versatile synthesis procedure could be adapted for making fluorescent probes for the assay of other glycoside hydrolases.
| S-EPMC7611149 | biostudies-literature
Project description:OBJECTIVES:The aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation. BACKGROUND:Polarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure. METHODS:Thirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model. RESULTS:The median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD. CONCLUSIONS:Intravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.
| S-EPMC7241775 | biostudies-literature
Project description:This paper describes a new class of ultrafast dynamic spectro-polarimetry based on a specially designed one-piece polarizing interferometer. It provides spectral polarimetric parameters of an anisotropic object in milliseconds with high precision. The proposed ultrafast spectro-polarimetry has no moving parts and it is highly robust to external noises. The one-piece polarizing interferometric scheme enables the world fastest and simplest solution in spectroscopic polarimetry. The distinct simple concept on one-piece polarizing interferometer can extract spectroscopic polarimetric parameters Ψ(k) and Δ(k) precisely with a speed of over 200 Hz over the entire visible wavelength range with a spectral resolution of less than 1 nm. The proposed novel one-piece scheme will have a significant potential of a paradigm shift from lab to fab in polarization metrology.
| S-EPMC6461686 | biostudies-literature
Project description:Chiral analysis is central for scientific advancement in the fields of chemistry, biology, and medicine. It is also indispensable in the development and quality control of chiral compounds in the chemical and pharmaceutical industries. Here, we present the concept of absolute optical chiral analysis, as enabled by cavity-enhanced polarimetry, which allows for accurate unambiguous enantiomeric characterization and enantiomeric excess determination of chiral compounds within complex mixtures at trace levels, without the need for calibration, even in the gas phase. Our approach and technology enable the absolute postchromatographic chiral analysis of complex gaseous mixtures, the rapid quality control of complex mixtures containing chiral volatile compounds, and the online in situ observation of chiral volatile emissions from a plant under stress.
| S-EPMC9166628 | biostudies-literature