G4 Form Research Articles

Solvation Structure with Enhanced Anionic Coordination for Stable Anodes in Lithium‐Oxygen Batteries

AbstractLi‐O2 batteries have garnered much attention due to their high theoretical energy density. However, the irreversible lithium plating/stripping on the anode limits their performance, which has been paid little attention. Herein, a solvation‐regulated strategy for stable lithium anodes in tetraethylene glycol dimethyl ether (G4) based electrolyte is attempted in Li‐O2 batteries. Trifluoroacetate anions (TFA−) with strong Li+ affinity are incorporated into the lithium bis(fluorosulfonyl)imide (LiTFSI)/G4 electrolyte to attenuate the Li+‐G4 interaction and form anion‐dominant solvates. The bisalt electrolyte with 0.5 M LiTFA and 0.5 M LiTFSI mitigates G4 decomposition and induces an inorganic‐rich solid electrolyte interphase (SEI). This contributes to decreased desolvation energy barrier from 58.20 to 46.31 kJ mol−1, compared with 1.0 M LiTFSI/G4, for facile interfacial Li+ diffusion and high efficiency. It yields extended lifespan of 120 cycles in Li‐O2 battery with a limited Li anode (7 mAh cm−2). This work gains comprehensive insights into rational electrolyte design for Li‐O2 batteries.

Solvation Structure with Enhanced Anionic Coordination for Stable Anodes in Lithium-Oxygen Batteries.

Li-O2 batteries have garnered much attention due to their high theoretical energy density. However, the irreversible lithium plating/stripping on the anode limits their performance, which has been paid little attention. Herein, a solvation-regulated strategy for stable lithium anodes in tetraethylene glycol dimethyl ether (G4) based electrolyte is attempted in Li-O2 batteries. Trifluoroacetate anions (TFA-) with strong Li+ affinity are incorporated into the lithium bis(fluorosulfonyl)imide (LiTFSI)/G4 electrolyte to attenuate the Li+-G4 interaction and form anion-dominant solvates. The bisalt electrolyte with 0.5 M LiTFA and 0.5 M LiTFSI mitigates G4 decomposition and induces an inorganic-rich solid electrolyte interphase (SEI). This contributes to decreased desolvation energy barrier from 58.20 to 46.31 kJ mol-1, compared with 1.0 M LiTFSI/G4, for facile interfacial Li+ diffusion and high efficiency. It yields extended lifespan of 120 cycles in Li-O2 battery with a limited Li anode (7 mAh cm-2). This work gains comprehensive insights into rational electrolyte design for Li-O2 batteries.

Shifting the Triangle-Square Equilibrium of Self-Assembled Metallocycles by Guest Binding with Enhanced Photosensitization.

Shifting a triangle-square equilibrium in one direction is an important problem in supramolecular self-assembly. Reaction of a benzothiadiazole-based diimidazole donor with a cis-Pt(II) acceptor yielded an equilibrium mixture of a triangle ([C18H24N10O6S1Pt1]3≡ PtMCT) and a square ([C18H24N10O6S1Pt1]4≡ PtMCS). We report here the shifting of such equilibrium toward a triangle using a guest (pyrene aldehyde, G1). While both benzothiadiazole and pyrene aldehyde can form reactive oxygen species (ROS) in organic solvents, their therapeutic use in water is restricted due to aqueous insolubility. The enhanced water solubility of the benzothiadiazole unit and G1 by macrocycle formation and host-guest complexation, respectively, enabled enhanced ROS generation by the host-guest complex (G1' ⊂ PtMCT) in water (G1' = hydrated form of G1). The guest-encapsulated metallacycle (G1' ⊂ PtMCT) has shown synergistic antibacterial activity compared to the mixture of macrocycles upon white-light irradiation due to enhanced ROS generation. The mechanism for such enhanced activity was established by measuring the oxidative stress and relative internalization of PtMCs and G1' ⊂ PtMCT.

Regulation of acetylcholinesterase during the lipopolysaccharide-induced inflammatory responses in microglial cells.

The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of α7 nicotinic acetylcholine receptor (α7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, α7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-κB and cAMP signaling. Moreover, ACh or α7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating α7 nAChR and followed by the regulation of NF-κB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system.

Anti-acetylcholinesterase activity of Corallocarpus epigaeus tuber: In vitro kinetics, in silico docking and molecular dynamics analysis

Biological activities of Corallocarpus epigaeus tuber (CET) were determined and its active constituents were identified. CET was sequentially extracted with various solvents. The methanol extract was further fractionated using silica coloumn chromatography to obtain active constituents-rich fraction called CET-MAF. The phytochemicals in CET-MAF was identified using GC-MS analysis. The in vitro antioxidant activity and inhibition against various globular forms of acetylcholinesterase (AChE) by CET-MAF were determined. In silico analysis of CET-MAF active constituents interaction with human AChE was carried out. CET-MAF showed in vitro antioxidant activity. CET-MAF inhibited various globular forms of AChE, G1 (IC50 = 147 µg/ml; Ki=13.6 µg/ml), G2 (IC50=146 µg/ml; Ki=8.6 µg/ml) and G4 (IC50 = 158 µg/ml; Ki = 9.3 µg/ml) in mixed manner. Molecular docking analysis revealed the interaction of active constituents such as 5-acetoxypentadecane (5AP) and alpha-linolenic acid (ALA) of CET-MAF with active site of AChE. Molecular dynamics simulation for 500 ns revealed the stable binding of these compounds with AChE. MMBGSA calculation revealed the binding energy of -52.95 and -55.49 kcal/mol for interaction of ALA and 5AP with AChE, respectively. Altogether, CET-MAF showed biological activities in vitro which can be used against cognitive dysfunction.

Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease.

ABSTRACTPeople of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction of this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting two copies of these APOL1 risk variants, known as G1 and G2, causes high rates of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy and hypertension-associated end-stage kidney disease. Disease risk follows a recessive mode of inheritance, which is puzzling given the considerable data that G1 and G2 are toxic gain-of-function variants. We developed coisogenic bacterial artificial chromosome (BAC) transgenic mice harboring either the wild-type (G0), G1 or G2 forms of human APOL1. Expression of interferon gamma (IFN-γ) via plasmid tail vein injection results in upregulation of APOL1 protein levels together with robust induction of heavy proteinuria and glomerulosclerosis in G1/G1 and G2/G2 but not G0/G0 mice. The disease phenotype was greater in G2/G2 mice. Neither heterozygous (G1/G0 or G2/G0) risk variant mice nor hemizygous (G1/−, G2/−) mice had significant kidney injury in response to IFN-γ, although the heterozygous mice had a greater proteinuric response than the hemizygous mice, suggesting that the lack of significant disease in humans heterozygous for G1 or G2 is not due to G0 rescue of G1 or G2 toxicity. Studies using additional mice (multicopy G2 and a non-isogenic G0 mouse) supported the notion that disease is largely a function of the level of risk variant APOL1 expression. Together, these findings shed light on the recessive nature of APOL1-nephropathy and present an important model for future studies.

Influence of the 5\u2032-terminal sequences on the 5\u2032-UTR structure of HIV-1 genomic RNA

The 5′-UTR of HIV-1 genomic RNA is known to form specific structures and has important functions. There are three 5′-terminal sequences, G1, G2 and G3, with different localizations in the cell and virion particles as well as different efficiencies in translation and reverse transcription reactions. In the present study, the structural characteristics of the joint region between the TAR and PolyA stems was analysed, and it was found that small differences in the 5′-terminus affect the conformational characteristics of the stem-loop structures. In the G1 form, the two stems form a coaxial stem, whereas in the G2 and G3 forms, the two stems are structurally independent of each other. In the case of the G1 form, the 3′-flanking nucleotides of the PolyA stem are included in the stable coaxial stem structure, which may affect the rest of the 5′-UTR structure. This result demonstrates that the local conformation of this functionally key region has an important role in the function of the 5′-UTR.

Combined spectroscopic and theoretical analysis of the binding of a water-soluble perylene diimide to DNA/RNA polynucleotides and G-quadruplexes

We present here a combined spectroscopic and theoretical analysis of the binding of N,N’-bis(2-(1-piperazino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide dichloride (PZPERY) to different biosubstrates. Absorbance titrations and circular dichroism experiments, melting studies and isothermal calorimetry (ITC) titrations reveal a picture where the binding to natural double-stranded DNA is very different from that to double and triple-stranded RNAs (poly(A)∙poly(U) and poly(U)∙poly(A)⁎poly(U)). As confirmed also by the structural and energetic details clarified by density functional theory (DFT) calculations, intercalation occurs for DNA, with a process driven by the combination of aggregates disruption and monomers intercalation. Oppositely, for RNAs, no intercalation but groove binding with the formation of supramolecular aggregates is observed. Among all the tested biosubstrates, the affinity of PZPERY towards DNA G-quadruplexes (G4) is the greatest one with a preference for human telomeric G4s. Focusing on hybrid G4 forms, either sitting-atop (“tetrad-parallel”) or lateral (“groove-parallel”) binding modes were considered in the discussion of the experimental results and molecular dynamics (MD) simulations. Both turned out to be possible concurrently, in agreement also with the experimental binding stoichiometries higher than 2:1.

In vitro and in silico analysis of novel astaxanthin-s-allyl cysteine as an inhibitor of butyrylcholinesterase and various globular forms of acetylcholinesterases

In Alzheimer's disease (AD) and diabetes-associated cognitive decline, the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity is increased. AChE exists as different globular molecular forms: tetramer (G4), dimer (G2) and monomer (G1). In adult brain, G4 form is abundant however in AD, the ratio of lower molecular forms (G1) to G4 form increased. Hence, the present study delineated the inhibition of novel astaxanthin-s-allyl cysteine (AST-SAC) against BChE and various molecular forms of AChE. Cobra venom, human erythrocyte and Electrophorus electricus was used as source of G1, G2 and G4 form of AChE. AST-SAC showed inhibition against G1 (IC50 = 0.72 μM, competitive, Ki = 0.66 μM), G2 (IC50 = 0.65 μM, mixed, Ki = 0.50 μM) and G4 (IC50 = 0.67 μM, competitive, Ki = 0.67 μM) form of AChE. AST-SAC inhibited human brain AChE (IC50 = 0.84 μM, competitive, Ki = 0.53 μM) and human serum BChE (IC50 = 0.80 μM, competitive, Ki = 0.58 μM). In silico analysis revealed the interaction of AST-SAC with the amino acids present in peripheral anionic and catalytic site of human AChE and BChE. Molecular dynamics simulation confirmed the stable interaction of AST-SAC in the active site gorge of AChE and BChE.

Effect of structure levels on surface-enhanced Raman scattering of human telomeric G-quadruplexes in diluted and crowded media

Human telomeric G-quadruplexes are emerging targets in anticancer drug discovery since they are able to efficiently inhibit telomerase, an enzyme which is greatly involved in telomere instability and immortalization process in malignant cells. G-quadruplex (G4) DNA is highly polymorphic and can adopt different topologies upon addition of electrolytes, additives, and ligands. The study of G-quadruplex forms under various conditions, however, might be quite challenging. In this work, surface-enhanced Raman scattering (SERS) spectroscopy has been applied to study G-quadruplexes formed by human telomeric sequences, d[A3G3(TTAGGG)3A2] (Tel26) and d[(TTAGGG)4T2] (wtTel26), under dilute and crowding conditions. The SERS spectra distinctive of hybrid-1 and hybrid-2 G-quadruplexes of Tel26 and wtTel26, respectively, were observed for the sequences folded in the presence of K+ ions (110mM) in a buffered solution, representing the diluted medium. Polyethylene glycol (5, 10, 15, 20, and 40% v/v PEG) was used to create a molecular-crowded environment, resulting in the formation of the parallel G-quadruplexes of both studied human telomeric sequences. Despite extensive overlap by the crowding agent bands, the SERS spectral features indicative of parallel G4 form of Tel26 were recognized. The obtained results implied that SERS of G-quadruplexes reflected not only the primary structure of the studied human telomeric sequence, including its nucleobase composition and sequence, but also its secondary structure in the sense of Hoogsteen hydrogen bonds responsible for the guanine tetrad formation, and finally its tertiary structure, defining a three-dimensional DNA shape, positioned close to the enhancing metallic surface. Graphical abstract.

ρ-Meson properties in medium

Properties of ρ-meson in symmetric nuclear matter are investigated in a light-front constituent quark model (LFCQM), using the in-medium inputs calculated by the quark–meson coupling (QMC) model. The LFCQM used in this study was already applied for the studies of the electromagnetic properties of ρ-meson in vacuum, namely, the charge G0, magnetic G1, and quadrupole G2 form factors, electromagnetic charge radius, and electromagnetic decay constant. Using the two different density dependence of the regulator mass in medium, we predict that the charge radius, and quadrupole moment are enhanced as increasing the nuclear matter density, while the magnetic moment is slightly quenched. Furthermore, we predict the value Qzero2, which crosses zero of the charge form factor, G0(Qzero2)=0 (Q2=−q2>0 with q being the four-momentum transfer), decreases as increasing the nuclear matter density by the two different density dependence of the regulator mass. On the other hand, for the electromagnetic decay constant of the ρ-meson, the two different density dependence of the regulator mass predict the opposite density dependence. Namely, as increasing the nuclear matter density, the naive treatment with the density independent regulator mass as in the vacuum, predicts the increase of the decay constant, while the other that assumes the same density dependence of the regulator mass as that of the in-medium constituent quark mass, predicts the decrease of the decay constant. Thus, although the other physical quantities are predicted to have similar density dependence by the two different density dependence of the regulator mass applied, the density dependence of the ρ-meson electromagnetic decay constant is predicted to have opposite density dependence, and the facts suggest that the in-medium ρ-meson decay constant needs to be investigated further in the future.

Compact Solvmanifolds with a Closed G<sub>2</sub>-Structure

We consider a parametrized family of compact G2-calibrated solvmanifolds, and construct associative (so volume-minimizing submanifolds) 3-tori with respect to the closed G2-structure. We also study the Laplacian flow of this closed G2 form on the solvable Lie group underlying to each of these solvmanifolds, and show long time existence of the solution.

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study.

Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Role of Combined 68Ga-DOTATOC and 18F-FDG Positron Emission Tomography/Computed Tomography in the Diagnostic Workup of Pancreas Neuroendocrine Tumors: Implications for Managing Surgical Decisions.

Ga-DOTATOC (Ga) positron emission tomography (PET)/computed tomography (CT) is recommended in the workup of pancreas neuroendocrine tumors (PanNETs); evidence suggests that F-FDG (F) PET/CT can also provide prognostic information. Aims of this study were to assess the role of combined Ga- and F-PET/CT in the evaluation of grade (G) 1-2 PanNETs and to test the correlation between F-PET/CT positivity and tumor grade. Preoperative Ga- and F-PET/CT of 35 patients with surgically resected G1-2 PanNETs were evaluated. For grading, the 2010 World Health Organization Classification was used; an ancillary analysis with Ki67 cutoffs at 5% to 20% was conducted. Correlation between F-PET/CT positivity (SUVmax > 3.5) and grade was assessed. Of 35 PanNETs, 28.6% and 71.4% were G1 and G2 as per World Health Organization. Ga-PET/CT showed high sensitivity (94.3%) in detecting G1-2 PanNETs. F-PET/CT was positive in 20% and 76% G1 and G2 tumors (P = 0.002). F-PET/CT identified G2 PanNETs with high positive predictive value (PPV, 90.5%). F-PET/CT correlated with tumor grade also in the ancillary analysis (P = 0.009). The high sensitivity of Ga-PET/CT in NET detection is known. The high PPV of F-PET/CT in the identification of G2 forms suggests its potential role in PanNETs prognostication and risk stratification.

Acetylcholinesterase inhibitor modifications: a promising strategy to delay the progression of Alzheimer's disease.

Alzheimer's disease (AD), a fatal, progressive, neurodegenerative disorder, is the most common cause of old-age dementia, accounting for 50–75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disorientation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care (World Alzheimer Report, 2013).

Serum Immunoglobulin G4 levels are elevated in patients with Graves' ophthalmopathy.

Recent studies have shown close association between serum Immunoglobulin G4 (IgG4) levels and forms of autoimmune thyroiditis. However, there are limited data about the relationship between IgG4 and Graves' ophthalmopathy (GO). In the present study, we aimed to determine the possible association between IgG4 and GO. Cross-sectional study. Sixty-five patients with Graves' disease (GD) and 25 healthy controls were recruited into the study. Thirty-two of these patients had GO. Serum IgG4 levels, thyroid functions and thyroid volumes were measured in all participants. Ophthalmological examination including Hertel's exophthalmometer readings (HER), Schirmer's test (ST), 'NO SPECS' classification and clinical activity score evaluation (CAS) were performed to all patients with GD. IgG4 levels were significantly elevated in patients with Graves' disease compared to controls (P = 0·0001). Also, IgG4 levels were significantly higher in patients with and without GO when compared to control subjects (P = 0·0001 and P = 0·002, respectively). Furthermore, IgG4 levels were significantly higher in the GO group compared with GD patients without GO (P = 0·024). IgG4 levels were observed to increase in parallel to CAS. Compared with other GD patients, 15 GD patients with serum IgG4 levels ≥ 135 mg/dl had higher CAS scores (P = 0·012). None of the factors including, TSH, T3, T4 levels, thyroid volume, HER and ST measurements, affect IgG4 levels as an independent factor. IgG4 levels are evidently increased in patients with GD, and there is a possible relationship between IgG4 and GO. Our results suggest that IgG4 may be helpful in screening GD patients with high risk for GO and may well become a good indicator for the selection of right medication in the future.

Effective and less toxic trimodality approach in muscle invasive urinary bladder cancer.

e15505 Background: Bladder cancer represents a global health problem. Radical cystectomy considered the standard of care for invasive bladder cancer. Because of the potential morbidity with surgery, organ preservation via trimodality approach has been the subject of investigation. The concurrent use of cisplatin with 5-FU or gemcitabin with local radiotherapy has been studied and the results were better than radical cystectomy. However, this was associated with grade 3-4 (G3-4) toxicity. Recently, similarly effective but less toxic regimen by the use of paclitaxel and cisplatin is under investigation. Methods: We proposed a single-center, single arm, phase II prospective cohort study. 30 patients (22 male and 8 female) with T2-T3 bladder cancer according to the AJCC 2010 were included. All patients were >18y with exclusion of those with bladder capacity < 350cc, hydronephrosis, with previous intravesical therapy, systemic chemotherapy or pelvic radiation, those currently receiving nephrotoxic or ototoxic drugs, and those with other malignancies. All patients treated with maximum transurethral resection (TUR) followed by local radiotherapy 64Gy concurrently with weekly 60mg/m2 Paclitaxel and 20mg/m2 Cisplatin. Results: Cystoscopic re-evaluation 6-8 weeks after the end of treatment revealed that 90% of patients achieve complete response (CR), 6.7% achieve partial response (PR) and 3.3% had stable disease (SD). Mild toxicity was infrequent and easily controlled without interruption of treatment except in one patient. Toxicity was in the form of cystitis G1 in 46.7% and G2 in 3.3%. Diarrhea G1 in 33.3% and G2 in 3.3%. Only one patient who has past history of piles, developed G2 proctitis that leads to irregularity of treatment. Other mild toxicities were: G1 dermatitis (80%), G1 bleeding per rectum (3.3%), G1 anemia (13.3%), G1 and G2 nausea and vomiting (50% and 33.3% respectively), while neutropenia and thrompocytopenia were not seen. Conclusions: Our preliminary results revealed that weekly low dose paclitaxel and cisplatin concurrently with local radiotherapy was effective, tolerable and has acceptable toxicity in the treatment of muscle invasive urinary bladder cancer.

Calcium-sensitive Activity and Conformation of Caenorhabditis elegans Gelsolin-like Protein 1 Are Altered by Mutations in the First Gelsolin-like Domain

The gelsolin family of actin regulatory proteins is activated by Ca(2+) to sever and cap actin filaments. Gelsolin has six homologous gelsolin-like domains (G1-G6), and Ca(2+)-dependent conformational changes regulate its accessibility to actin. Caenorhabditis elegans gelsolin-like protein-1 (GSNL-1) has only four gelsolin-like domains (G1-G4) and still exhibits Ca(2+)-dependent actin filament-severing and -capping activities. We found that acidic residues (Asp-83 and Asp-84) in G1 of GSNL-1 are important for its Ca(2+) activation. These residues are conserved in GSNL-1 and gelsolin and previously implicated in actin-severing activity of the gelsolin family. We found that alanine mutations at Asp-83 and Asp-84 (D83A/D84A mutation) did not disrupt actin-severing or -capping activity. Instead, the mutants exhibited altered Ca(2+) sensitivity when compared with wild-type GSNL-1. The D83A/D84A mutation enhanced Ca(2+) sensitivity for actin severing and capping and its susceptibility to proteolytic digestion, suggesting a conformational change. Single mutations caused minimal changes in its activity, whereas Asp-83 and Asp-84 were required to stabilize Ca(2+)-free and Ca(2+)-bound conformations, respectively. On the other hand, the D83A/D84A mutation suppressed sensitivity of GSNL-1 to phosphatidylinositol 4,5-bisphosphate inhibition. The structure of an inactive form of gelsolin shows that the equivalent acidic residues are in close contact with G3, which may maintain an inactive conformation of the gelsolin family.

Tetra-2,3-pyrazinoporphyrazines with Externally Appended Pyridine Rings. 10. A Water-Soluble Bimetallic (ZnII/PtII) Porphyrazine Hexacation as Potential Plurimodal Agent for Cancer Therapy: Exploring the Behavior as Ligand of Telomeric DNA G-Quadruplex Structures

The behavior of a bimetallic water-soluble (Zn(II)/Pt(II)) porphyrazine hexacation as ligand of G-quadruplex (G4) structures adopted by a human telomeric DNA sequence has been examined with different spectroscopic techniques. In K(+) rich solution the hexacationic Zn(II) porphyrazine ligand bearing a peripheral cis-platin-like functionality changes the G-quadruplex conformational equilibrium of the human telomeric sequence 5'-d[AGGG(TTAGGG)(3)]-3' and drives it exclusively toward a very stable parallel G4 form in the complex with 2:1 stoichiometry. An increase of the melting temperature of more than 20 °C is observed in this complex compared to the G4 alone. On the contrary ligand binding to G-quadruplex of the same telomeric sequence in Na(+) rich solution neither markedly influences the predominant basket conformation nor confers increased thermal stability to the G4 structure.

Naturally occurring glycan forms of human immunoglobulins G1 and G2

High resolution glycan mapping was performed on human immunoglobulin G (IgG) obtained from individual healthy subjects and from a combined sample of healthy subjects. In addition to the commonly known complex glycans, a variety of minor glycans are described and quantified, including high mannose forms and several previously unreported hybrid forms. Fc specific glycan analysis was also performed through peptide mapping with LC/MS/MS. Differences in the glycan linked Fc peptide masses allowed glycan profiles to be analyzed and quantified from IgG1 and IgG2 simultaneously for each subject within the same sample. Glycan profiles differed between subtypes, with greater levels of more fully galactosylated species found on IgG1 (e.g. G2F, SG2F) than IgG2. These results also show that Gal attachment on G1F is biased to the Man (α1 → 6) arm for IgG1 and on the Man (α1 → 3) arm for IgG2 from individual healthy subjects.