Effect Of Macromolecules Research Articles

Neurochemical correlations in short echo time proton magnetic resonance spectroscopy.

Neurochemical concentrations determined by magnetic resonance spectroscopy (MRS) have been treated as statistically independent measurements in various clinical MRS studies. However, spectral overlap, independent of any biological effects, could lead to significant correlations between neurochemical concentrations extracted from spectral fitting of MRS data, confounding determination of correlations of biological origin. Short echo time (TE) proton MRS spectra are very crowded because of the comparatively narrow chemical shift dispersion of proton nuclear spins. In this study, the complex neurochemical correlations of spectral origin in short-TE MRS spectra were quantified. The effects of macromolecules and the background spectral baseline on metabolite-metabolite correlations were also analyzed. Our results demonstrate the importance of factoring in spectral correlations when correlating overlapping metabolite signals in short-TE spectra with clinical parameters.

Colloidal stability and aggregation behavior of CdS colloids in aquatic systems: Effects of macromolecules, cations, and pH

Redox-dynamic environments such as river floodplains and paddy fields have been demonstrated to be important sources of CdS colloids. To date, the aggregation kinetics of CdS colloids had not yet been studied, and the structure and properties of macromolecules on the interaction between different macromolecules and CdS colloids, as well as the aggregation behavior of CdS colloids are unclear. This study investigated the colloidal stability of CdS colloids in model aqueous systems with various solution chemistry and representative of macromolecules. The results showed that increased electrolyte concentration destabilized CdS colloids by charge screening, with the cationic effect following Ca2+ > Mg2+ > K+ > Na+; Higher solution pH stabilized CdS colloids by raising the critical coagulation concentration from 33 to 56 mM NaCl. Electron microscopy and spectroscopy verified the strong interaction between macromolecules and CdS colloids, and macromolecule adsorbed on the surface of CdS to form a protective layer called “NOM corona”. The interaction between macromolecules and CdS induced distinct aggregation behaviors in NaCl and CaCl2 solutions. The steric repulsion generated by “NOM corona” significantly stabilized CdS colloids in NaCl solution, and the stabilizing order was consistent with the adsorbing capacity of macromolecules on CdS colloids, namely Bovine serum albumin (BSA) > sodium alginate (SA) > calf thymus DNA (DNA) > Suwannee River humic acid (HA). BSA and DNA also inhibited CdS colloids aggregation in the CaCl2 solution due to the balance of steric hindrance, cation bridging, and electrostatic repulsion. For HA and SA, Ca2+ bridging and EDL compression contributed to their destabilization of CdS colloids in CaCl2 solution. Macromolecules concentration affect corona formation that alter stability of CdS colloids. There results showed that the complex influences of solution chemistry and macromolecules on fate and transport of CdS colloids in environment. The findings will help to understand the potential risks of CdS colloids in environment.

Oral absorption and effect of macromolecules in traditional Chinese medicine: a new perspective and research mode of phase structure

Protein polypeptides and polysaccharides, the indispensable macromolecular active components in traditional Chinese medicine, are widely found in Chinese medicine decoction after the decoction of traditional Chinese medicine. However, through oral administration, these macromolecules are digested by the stomach and intestine and thus fail to be absorbed in prototype. This is inconsistent with the actual clinical efficacy of Chinese medicine decoction. According to modern research, new phase structures and effects of the macromolecules emerge during the decoction of traditional Chinese medicine, but the phase change law caused by the interaction among the components of traditional Chinese medicine and the relationship between phase structure and effect are still unclear. Thus, this study reviewed the oral absorption of macromolecular components of traditional Chinese medicine, analyzed the internal relationship of the form of macromolecules in traditional Chinese medicine with the absorption and effect based on phase structure, and summarized the research mode of oral absorption and effect of macromolecules in traditional Chinese medicine with phase structures as the core, providing new ideas and methods for future research.

Computational Methods for Protein Tertiary Structure Analysis.

Protein folding accuracy is fundamental to all cells. In spite of this, it is difficult to maintain the fidelity of protein synthesis and folding due to the fact that the implicit genetic and biochemical systems are inherently prone to error, which leads to the constant production of a certain amount of misfolded proteins. This problem is further compounded by genetic variation and the effects of environmental stress. To that end, the prediction of protein structures for tertiary protein structure analysis and prediction might be an ideal approach for the study of mutation effects in macromolecules and their complexes. With the development and accessibility to increasingly powerful computational systems, this type of study will enable a wide variety of opportunities for the creation of better-targeted peptide-based pharmacotherapy and prospects for precision medicine in future.

Research on Boundary Layer Effect in Fractured Reservoirs Based on Pore-Scale Models

It is of great significance to study the seepage characteristics of heavy oil reservoirs, which are conducive to the efficient development of resources. Boundary layer effect (BLE) exists in the pore-scale flow process of macromolecular fluid media, which is different from the flow law of conventional fluid in the pore, yet the influence of BLE is ignored in the previous pore-scale simulation. Conventional porous media simulations have difficulty analyzing the mass transfer law of small-scale models under the influence of microfractures. Based on the CT scanning data and thin section data of the real core in the target area, the rock skeleton and flow space were extracted according to the maximum ball algorithm, and the pore network model representing the complex structure was constructed. The microscale effect of macromolecules in the flow process in the pores was characterized by modifying the effective flow. The effects of the BLE on the effective connectivity, displacement process, and oil distribution law were analyzed. The seepage characteristics of different wettability conditions and different water cut stages were compared. The results show that BLE reduces the effective flow space and leads to deviations in the relative permeability curve and capillary curve. For fractured porous media, the irregular shape of porous media was characterized by the morphological method, and the mass transfer process was analyzed by the equivalent flux method. The influence of the porous media shape on the macromass transfer process was compared. This study provides a solution to the problem of BLE in pore-scale simulation.

Prediction of Tribological Parameters for Polymer Nanocomposites

The possibility for predicting tribological characteristics of polymer nanocomposites was studied with the example of nanocomposite poly (ether ketone)/graphene. It has been shown that the “escapement” effect of polymer matrix macromolecules by graphene surface essentially reduces (a several times) the indicated characteristics. The proposed simple structural model describes the obtained results through experiments. The fulfilled estimations indicate that the “escapement” effect of macromolecules by graphene surface results in a loss of 60–86% of the initial area of contact polymer matrix-nanofiller with a growth of graphene content up to 10 mas %. Thus, the improvement of the indicated contact (i.e., by nanofiller functionalization) likely leads to essential improvement of tribological characteristics of nanocomposite.

A pH Replica Exchange Scheme in the Stochastic Titration Constant-pH MD Method.

Solution pH is a physicochemical property that has a key role in cellular regulation, and its impact at the molecular level is often difficult to study by experimental methods. In this context, several theoretical methods were developed to study pH effects in macromolecules. The stochastic titration constant-pH molecular dynamics method (CpHMD) was developed by coupling molecular sampling methods, which are appropriate to study the conformational ensemble of biomolecules, with continuum electrostatics approaches, which properly describe pH-dependent protonation states. However, in difficult cases, the protonation sampling can be too slow for the commonly accessible computational times. In this work, we combined a pH replica exchange scheme with this CpHMD method and explored several optimization strategies and possible limitations.

Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles

In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated. Herein, ectopic subcutaneous tumor models presenting different tumor microenvironments were established by inoculation of SCC7, U87, HT29, PC3, and A549 cancer cell lines into athymic nude mice, respectively. In the five different types of tumor-bearing mice, tumor-targeted delivery of self-assembled glycol chitosan nanoparticles (CNPs) were comparatively evaluated to identify the correlation between the tumor microenvironments and targeted delivery of CNPs. As a result, neovascularization and extents of intratumoral extracellular matrix (ECM) were both important in determining the tumor targeted delivery of CNPs. The EPR effect was maximized in the tumors which include large extent of angiogenic blood vessels and low intratumoral ECM content. This comprehensive study provides substantial evidence that the EPR effects based tumor-targeted delivery of nanoparticles can be different depending on the tumor microenvironment in individual tumors. To overcome current limitations in clinical nanomedicine, the tumor microenvironment of the patients and EPR effects in clinical tumors should also be carefully studied.

Effects of Molecular Crowding on the Binding Affinity of Dihydrofolate for Dihydrofolate Reductase

The reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) by the enzyme dihydrofolate reductase (DHFR), using NADPH as a cofactor, is an essential part of the folate cycle. The inhibition of DHFR leads to interruption of DNA synthesis and consequently cell death, making this enzyme a crucial target in the treatment of cancer and other diseases. Previous studies examined the effects of small molecule osmolytes on the substrate interactions with two non-homologous DHFRs, E. coli chromosomal DHFR (EcDHFR) and R67 DHFR, with vastly different active site structures. The results indicated that DHF weakly interacts with the osmolytes in solution, shifting the binding equilibrium from DHF bound to DHFR to unbound DHF. It is hypothesized that similar weak, nonspecific interactions may also occur between cellular proteins and DHF. Weak interactions between cellular proteins and DHF would have consequences in vivo, where the concentration of the cellular milieu is approximately 300 g/L. Under the crowded conditions in the cell, there is a higher propensity for intermolecular interaction.Crowding effects of macromolecules in concentrations similar to those in vivo were examined. Isothermal titration calorimetry (ITC) and enzyme kinetic assays were used to detect effects of molecular crowders by monitoring activity of the (DHFR)-NADPH or DHF complex and the ternary DHFR-DHF-NADPH complex in the presence of these crowders. To recreate the conditions of molecular crowding in vivo, the binding of the enzyme-ligand complexes in the presence of molecular weight crowding agents (lysozyme or casein) was examined. Analysis of the Kd's and Km's indicated a correlation between increased molecular crowding in the solution and weakened binding of the DHFR-substrate complexes. These findings indicate an importance of molecular crowding on EcDHFR activity in vivo.

A224 高分子の影響に基づ<赤血球集合現象のモデル化(A2-5 循環器系バイオメカニクス3)

A224 高分子の影響に基づ<赤血球集合現象のモデル化(A2-5 循環器系バイオメカニクス3)

2E01 高分子の影響に基づく赤血球集合現象のモデル化(GS10-1:循環器系の計算バイオメカニクス(1))

2E01 高分子の影響に基づく赤血球集合現象のモデル化(GS10-1:循環器系の計算バイオメカニクス(1))

Antigen-antibody selective recognition using LiTaO3SH-SAW sensors: investigations on macromolecules effects on binding kinetic constants

A gravimetric surface acoustic wave (SAW) biosensor, based on the biotin-streptavidin and antistreptavidin-streptavidin recognitions, has been carried out. A network analyser and a pulse excitation technique were used to monitor both amplitude and phase changes. The SAW biosensor presented a total selective recognition of streptavidin-antistreptavidin and HRPstreptavidin-antistreptavidin. The presence of HRP (Horseradish peroxidase) affects neither the selectivity nor the sensitivity (of order of 0.25°/nM) of the biosensor, nevertheless, it causes a reduction of binding kinetics by a factor ranging between 2 to 5, as well as a diminution of antistreptavidin saturation concentration (of 40%). Results showed that equilibrium constants can be different, depending on evaluation method (from saturation values or from linear part of the output signal variation according to solution concentration).

Nanostructural behavior aspects of macromolecules with different molecular architecture on interfaces

This work describes a new class of macromolecular compounds, i.e., acrylic acid and isobornyl acrylate gradient block copolymers synthesized by controlled radical polymerization. A series of these gradient block copolymers was compared with acrylic acid and isobornyl acrylate block copolymers with similar compositions to demonstrate the effect of copolymer molecular architecture and the intense mechanical effect on their surface interactions with particles of different nature in aqueous dispersion systems. The method of electrokinetic sonic amplitude revealed the architectural effect of macromolecules to their surface interaction the particles at various concentrations of polymer and calculated the parameters of polymer adsorption layers. The surface interaction models were suggested for macromolecules of block and gradient block copolymers of various compositions with hydrophilic and hydrophobic particles and the copolymer architecture was proven to determine the nanostructure of polymer adsorption layers on interface. The nanostructural differences were suggested and confirmed in the interaction of block and gradient block copolymers with interface of different nature.

Translational and Rotational Diffusion of a Small Globular Protein under Crowded Conditions

Protein-protein interaction is the fundamental step of biological signal transduction. Interacting proteins find each other by diffusion. To gain insight into diffusion under the crowded conditions found in cells, we used nuclear magnetic resonance spectroscopy (NMR) to measure the effects of solvent additives on the translational and rotational diffusion of the 7.4 kDa globular protein, chymotrypsin inhibitor 2. The additives were glycerol and the macromolecular crowding agent, polyvinyl pyrrolidone (PVP). Both translational diffusion and rotational diffusion decrease with increasing solution viscosity. For glycerol, the decrease obeys the Stokes-Einstein and Stokes-Einstein Debye laws. Three types of deviation are observed for PVP: the decrease in diffusion with increased viscosity is less than predicted, this negative deviation is greater for rotational diffusion, and the negative deviation increases with increasing PVP molecular weight. We discuss our results in terms of other studies on the effects of macromolecules on globular protein diffusion.

Pseudomatrix synthesis of polymer-metal nanocomposite sols: Interaction of macromolecules with metal nanoparticles

The experimental and theoretical data on the effect of macromolecules on the formation of a metal phase during reduction of metal ions in a polymer solution and on the aggregative stability of sols with a narrow size distribution of metal nanoparticles and their small average size are summarized and analyzed. It has been shown that owing to the cooperativity, reversibility, and selectivity of noncovalent interactions of sufficiently long macromolecules with nanoparticles, the dispersion phase of such sols may be regarded as a macromolecule-nanoparticle complex, which forms once a certain size of the particles is achieved and in which the growth of particles ceases. The process of sol synthesis may be regarded as pseudomatrix. The theoretical model developed for the pseudomatrix process of metal phase formation in polymer solutions, which adequately describes the experimental data, makes it possible to control the synthesis conditions of sols of polymer-metal nanocomposites with preset dimensional characteristics of nanoparticles and to govern the aggregative stability of sols.

Effect of macromolecules in solutions for vitrification of mature bovine oocytes

This study was designed to evaluate vitrification procedures for in vitro matured bovine oocytes for efficient blastocyst production after warming, IVF and culture. A second goal was to replace serum as the macromolecular component of the vitrification solution, without compromising efficacy. The first experiment compared two containers, open pulled straws (OPS) versus cryoloops, and two vitrification protocols: short equilibration (H-TCM-199 + 10% EG + 10% DMSO + 20% FCS for 30 s, followed by H-TCM-199 + 20% EG + 20% DMSO + 20% FCS + 0.48 M galactose for 20 s) versus long equilibration (H-TCM-199 + 3% EG + 20% FCS for 10 min, followed by H-TCM-199 + 31% EG + 20% FCS + 1 M galactose for 20 s). Subsequent experiments used only cryoloops and the short equilibration protocol to evaluate the effect of replacing FCS with defined macromolecules (BSA, Ficoll, PVP, and PVA) in vitrification solutions. Cryoloops were superior to OPS for vitrification of oocytes as determined by blastocyst production ( P < 0.05). The short and long vitrification protocols gave similar results. The presence of macromolecules in vitrification solutions for bovine oocytes was necessary for acceptable post-warming developmental capacity; 20% FCS, 1% and 2% BSA, 6% and 18% Ficoll, 6% and 20% PVP, 1% PVA, and the combinations of 18% Ficoll + 1% BSA, and 6% PVP + 1% BSA provided similar protection during vitrification of oocytes; development ranged from 14.8% to 23.0% blastocysts/oocyte, which was not different ( P > 0.05) from non-vitrified controls (26.9–34.0% blastocysts/oocyte). Too much (6%) and too little (0.3%) BSA, and 0.3% PVA for vitrification resulted in lower blastocyst production ( P < 0.05) relative to unvitrified oocytes.

Effect of macromolecules and triton X-100 on the triplet of aggregated chlorophyll in aqueous solution

Chlorophyll a (Chl a) in aqueous solution (2–6% acetone) is present as mono- and dihydrated aggregated forms which are characterized by specific ground state absorption spectra. The amount of dihydrated form is larger in the presence of macromolecules, such as bovine serum albumin (BSA), lysozime and polyvinyl alcohol (PVA), increasing from BSA to lysozime and PVA. Chl a in aqueous acetone with and without macromolecules is characterized by low fluorescence and the absence of triplet–triplet (T–T) absorption. The ratio of dihydrated to monohydrated forms is significantly influenced by triton X-100. For lower triton X-100 concentrations, i.e. smaller than the critical micelle concentration of 0.26 mM (cmc), dihydrated forms are converted into monohydrated in both aqueous acetone and the presence of BSA or lysozime. In the presence of PVA dihydrated forms appeared to be resistant to triton X-100 action. Moreover, for triton X-100 concentrations of 2–3 times higher than cmc the amount of these forms is increased with time. T–T absorption of both mono- and dihydrated Chl a aggregates was not detected in the presence of [triton X-100] < cmc. The lack of T–T absorption in aqueous acetone solution as well as in the presence of macromolecules implies that the triplet lifetime of the chlorophyll aggregates is short ( τ T<10 ns) and/or the quantum yield of intersystem crossing is small (<5×10 −3). The Chl a monomers start to be formed as solubilized in the micelle for [triton X-100] larger than cmc, showing substantial fluorescence and T–T absorption.

The Effect of Macromolecules on Foam Stability in Sodium Dodecyl Sulfate/Cetylpyridinium Bromide Mixtures

The effects of macromolecules, gelatin, and polyvinylpyrrolidone (PVP), on the properties of foam comprising sodium dodecyl sulfate (SDS) and cetylpyridinium bromide (CPDB) have been studied by measurements of foamability, foam stability, surface tension, and solution specific viscosity. The results indicate that foamability and foam stability are significantly improved when macromolecules are added into mixed systems. Both gelatin and PVP associate with SDS/CPDB surfactants and form aggregates. Electrostatic repulsion and steric stabilization between the two sides of the foam lamellae, due to aggregation, and prevention of drainage in the lamellae, achieved by the long chains of macromolecules are the reasons for increasing foamability and foam stability. The interactions between PVP and surfactants is weaker than those between gelatin and surfactants. The strongest association between macromolecules and surfactants occurs when the molar ratio of SDS/CPDB is 1:1. By comparing PVP with gelatin, the former is favored to increase foamability, and the latter is favored to increase foam stability.

Synthesis and characterization of a catalytic Antibody–HPMA copolymer-Conjugate as a tool for tumor selective prodrug activation

Selective chemotherapy remains a key issue for successful treatment in cancer therapy. The use of targeting approaches like the enhanced permeability and retention (EPR) effect of macromolecules, is consequently needed. Here, we report the preparation of a novel catalytic antibody–polymer conjugate for selective prodrug activation. HPMA copolymer was conjugated to catalytic antibody 38C2 through an amide bond formation between ε-amino group of lysine residue from the antibody molecule and a p-nitrophenyl ester of the polymer. The conjugate was purified over a size exclusion column using FPLC. In the isolated fraction, one or two molecules of polymer were conjugated to one molecule of antibody based on gel analysis. The resulting conjugate retained most of its catalytic activity (75–81%) in comparison to the free antibody. The activity was monitored with a fluorogenic substrate and a prodrug activation assay using HPLC. Furthermore, the conjugate was evaluated in vitro for its ability to activate an etoposide prodrug using two different cancer cell lines. Cells growth inhibition using the prodrug and the conjugate was almost identical to inhibition by the free antibody and the prodrug. For the first time, a catalytic antibody was conjugated to a passive targeting moiety while retaining its catalytic ability to activate a prodrug. The conjugate described in this work can be used for selective activation of prodrug in the PDEPT (polymer directed enzyme prodrug therapy) approach by replacing the enzyme component with catalytic antibody 38C2.

Principles and applications of cross-correlated relaxation in biomolecules

In liquid-state NMR, spin relaxation due to cross-correlation of two anisotropic spin interactions can provide useful information about molecular structure and dynamics. These effects are manifest as differential line widths or line intensities in the NMR spectra. Recently, new experiments were developed for the accurate measurement of numerous cross-correlated relaxation rates in scalar coupled multi-spin systems. The recently introduced concept of transverse relaxation optimized spectroscopy (TROSY) is also based on cross-correlated relaxation. The present article outlines the basic concepts and experimental techniques necessary for understanding and exploiting cross-correlated relaxation effects in macromolecules. In addition, representative examples illustrate the potential of cross-correlated relaxation for high resolution NMR studies of proteins and nucleic acids. © 2000 John Wiley & Sons, Inc. Concepts Magn Reson 12: 207–229, 2000.