scholarly journals Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP

2018 ◽  
Author(s):  
C. Gupta ◽  
Y. Ren ◽  
B. Mertz

ABSTRACTPeptides with the ability to bind and insert into the cell membrane have immense potential in biomedical applications. pH (Low) Insertion Peptide (pHLIP), a water-soluble polypeptide derived from helix C of bacteriorhodopsin, can insert into a membrane at acidic pH to form a stable transmembrane α-helix. The insertion process takes place in three stages: pHLIP is unstructured and soluble in water at neutral pH (state I), unstructured and bound to the surface of a membrane at neutral pH (state II), and inserted into the membrane as an α-helix at low pH (state III). Using molecular dynamics (MD) simulations, we have modeled state II of pHLIP and a fast-folding variant of pHLIP, in which each peptide is bound to a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer surface. Our results provide strong support for recently published spectroscopic studies, namely that pHLIP preferentially binds to the bilayer surface as a function of location of anionic amino acids and that backbone dehydration occurs upon binding. Unexpectedly, we also observed several instances of segments of pHLIP folding into a stable helical turn. Our results provide a molecular level of detail that is essential to providing new insights into pHLIP function and to facilitate design of variants with improved cell-penetrating capabilities.

2013 ◽  
Vol 305 (9) ◽  
pp. G601-G610 ◽  
Author(s):  
Hamid M. Said

This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamin (WSV) transport in the large intestine and pancreas, two important organs of the digestive system that have only recently received their fair share of attention. WSV, a group of structurally unrelated compounds, are essential for normal cell function and development and, thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenously; rather, WSV are obtained from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source and a bacterial source (i.e., WSV generated by the large intestinal microbiota). Contribution of the latter source to human nutrition/health has been a subject of debate and doubt, mostly based on the absence of specialized systems for efficient uptake of WSV in the large intestine. However, recent studies utilizing a variety of human and animal colon preparations clearly demonstrate that such systems do exist in the large intestine. This has provided strong support for the idea that the microbiota-generated WSV are of nutritional value to the host, and especially to the nutritional needs of the local colonocytes and their health. In the pancreas, WSV are essential for normal metabolic activities of all its cell types and for its exocrine and endocrine functions. Significant progress has also been made in understanding the mechanisms involved in the uptake of WSV and the effect of chronic alcohol exposure on the uptake processes.


Author(s):  
Junqi Lin ◽  
Xin Chen ◽  
Nini Wang ◽  
Shanshan Liu ◽  
Yanmei Chen ◽  
...  

Transition metal clusters have been used for water oxidation with high catalytic efficiency. However, they are water soluble and often used homogeneously rather than heterogeneously. Herein, a water soluble octanuclear...


2005 ◽  
Vol 09 (02) ◽  
pp. 94-108 ◽  
Author(s):  
Patrícia S. Santiago ◽  
Shirley C. M. Gandini ◽  
Marcel Tabak

Interactions of cationic FeTMPyP with ionic and nonionic micelles have been studied by optical absorption, resonance light scattering (RLS) and 1 H NMR spectroscopies. The equilibrium behavior of FeTMPyP as a function of pH is described by several species in aqueous solution. The presence of phosphate anions leads to the existence of additional species in the acid p H region, probably due to the coordination of phosphates to the iron. FeTMPyP solution as a function of pH in the presence of anionic SDS showed a simplified equilibrium in acidic pH region, favoring the transition to the dimeric species. Titration of FeTMPyP as a function of SDS surfactant concentration showed the presence of three different porphyrin species: free metalloporphyrin monomers (or dimers depending on pH), metalloporphyrin monomers (or dimers) bound to the micelles, and nonmicellar metalloporphyrin/surfactant aggregates. In the case of zwitterionic LPC and HPS, and nonionic TRITON X-100 the nonmicellar metalloporphyrin/surfactant aggregates were not observed. Binding constants were calculated from optical absorption data and have values of 2 × 103 M −1 for SDS being much smaller for HPS (58 M −1), LPC and TRITON X-100. Comparison with our previous data for anionic FeTPPS 4 shows that both the electrostatic factor and hydrophobic forces are relevant in the porphyrin-surfactant interaction: for FeTPPS 4 binding constants to cationic CTAC and zwitterionic HPS are of the same order of magnitude, 1-3 × 104 M −1; for FeTMPyP the delocalization of the positive charges from the periphery substituents into the macrocycle ring leads to reduction of both electrostatic attraction to the micelle as well as hydrophobic character of the porphyrin ring, leading to a 10-fold reduction of binding to the micelles of opposite charge to the porphyrin. NMR data indicated that FeTMPyP is bound to the micelles as an equilibrium of two forms of monomer at pH 2.0, and at pH 9.0 the bound aggregated form (possibly dimers) is observed predominantly with some amount of a monomeric form.


2012 ◽  
Vol 550-553 ◽  
pp. 1681-1686 ◽  
Author(s):  
Jian Zeng ◽  
Ke Fu Chen ◽  
Jian Ping Xie ◽  
Guang Xu ◽  
Jun Li ◽  
...  

Tobacco stem and tobacco dust are the major raw materials in the reconstituted tobacco production. The extraction of the components from these materials is one of the most important procedures in making the reconstituted tobacco sheet. In this paper, we reported an approach of three-stage counter current extraction to transfer the components from tobacco stem and tobacco dust. The results showed that the extraction ratios for tobacco stem and tobacco dust were 40.2% and 54.2%, respectively. The testing results on the extracted tobacco stem and tobacco dust showed that the overall extraction ratios of water soluble sugars, total alkaloid, and chloride in tobacco dust were 89.3%, 90.5% and 100%, respectively; and the overall extraction ratios of water soluble sugars, total alkaloid and chloride in tobacco stem were 59.3%, 60.3% and 76.2%, respectively; The contents of total nitrogen in tobacco dust and tobacco stem were basically no change after each extraction. Lower extraction yield and higher extraction ration were obtain by three stages extract than those by single stage extract.


2009 ◽  
Vol 138 (2) ◽  
pp. 563-571 ◽  
Author(s):  
Youqiang Chen ◽  
Hua Bai ◽  
Qi Chen ◽  
Chun Li ◽  
Gaoquan Shi

Graft copolymers of acrylic monomers with cotton cellulose were obtained. The dependence of the degree and efficiency of grafting of acrylic acid and methyl methacrylate to cellulose on the concentration of monomer and initiator was investigated. Pre-adsorption of the initiator in the macromolecules of cellulose leads to an increase in the efficiency of the grafting. The efficiency of grafting is higher in those systems in which the initiator used is insoluble in the monomer solvent. Absorption of cellulose with an aqueous solution of the initiator - potassium persulfate, followed by removal of water was done. The advantage of using a water-soluble initiator is that during subsequent processing with a solution of monomer in an organic solvent, the desorption of the active centers does not occur. An increase in the concentration of theinitiator leads to an increase in the degree of grafting, a slight increase in the efficiency of the grafting, a significant decrease in the degree of polymerization and the molecular weight of the graft chains. In a heterogeneous process, an increase in the efficiency of grafting with an increase in the concentration of theinitiator is promoted by the additional adsorption interaction of the initiator molecules with the surface of cellulose. With an increase in the concentration of monomers, the overall degree of conversion slightly increases, the efficiency of grafting slightly decreases, the degree of grafting and the molecular weight of the graft chains increase significantly. The mechanism of graft copolymerization was investigated by comparative analysis of the IR and PMR spectra of cellulose, potassium persulfate, acrylic monomers and products of their interaction. Due to the results of spectroscopic studies, a scheme of graft copolymerization reactions has been proposed. The active centers of graft copolymerization are formed as a result of the reductive interaction of potassium persulfate, water and cellulose macromolecules.


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