Geometrical analysis of cytochrome c unfolding

A geometrical model has been developed to study the unfolding of iso-1 cytochrome c. The model draws on the crystallographic data reported for this protein. These data were used to calculate the distance between specific residues in the folded state, and in a sequence of extended states defined by n?=?3, 5, 7, 9, 11, 13, and 15 residue units. Exact calculations carried out for each of the 103 residues in the polypeptide chain demonstrate that different regions of the chain have different unfolding histories. Regions where there is a persistence of compact structures can be identified, and this geometrical characterization is fully consistent with analyses of time-resolved fluorescence energy-transfer (TrFET) data using dansyl-derivatized cysteine side-chain probes at positions 39, 50, 66, 85, and 99. The calculations were carried out assuming that different regions of the polypeptide chain unfold synchronously. To test this assumption, lattice Monte Carlo simulations were performed to study systematically the possible importance of asynchronicity. Calculations show that small departures from synchronous dynamics can arise if displacements of residues in the main body of the chain are much more sluggish than near-terminal residues.     

Affiliated subspaces and infiniteness of von Neumann algebras

We show that the structural properties of von Neumann algebra s are connected with the metric and order theoretic properties of various classes of affiliated subspaces. Among others we show that properly infinite von Neumann algebra s always admit an affiliated subspace for which (1) closed and orthogonally closed affiliated subspaces are different; (2) splitting and quasi‐splitting affiliated subspaces do not coincide. We provide an involved construction showing that concepts of splitting and quasi‐splitting subspaces are non‐equivalent in any GNS representation space arising from a faithful normal state on a Type I factor. We are putting together the theory of quasi‐splitting subspaces developed for inner product spaces on one side and the modular theory of von Neumann algebra s on the other side.     

Synthesis and antiviral activity of novel imidazo[2,1-b]thiazoles coupled with morpholine and thiomorpholines

Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio-morpholine coupled imidazo[2,1-b]thiazoles. The three-step reaction sequence involving the condensation of 1,3-dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α-bromoacetophenones yielded the desired imidazothiazoles 7(a–l) . Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC₅₀: 1.1 μM, C₅₀: >300 μM, SI = 273) and 7e (IC₅₀: 2.0 μM, C₅₀: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti-influenza hit analogs for further structural optimization.     

Modifications of 5,12-dihydroindolo[3,2-a]carbazole scaffold via its regioselective C2,9-formylation and C2,9-acetylation

The effective approaches for regioselective double formylation and acetylation of 5,12-dialkyl-6,7-diaryl-substituted 5,12-dihydroindolo[3,2-a]carbazoles by their treatment with dichloromethyl methyl ether in the presence of SnCl₄ or with acetyl chloride in the presence of AlCl₃ to afford the 2,9-diformyl or 2,9-diacetyl derivatives, respectively, were developed. Furthermore, new 2,9-bis(2,2-dicyanovinyl) derivatives were synthesized by the Knoevenagel condensation of diformyl-containing substrates with malononitrile, when new 2,9-bis(quinoxaline-2-yl)- and 2,9-bis(benzo[g]quinoxaline-2-yl) derivatives were formed via microwave-promoted oxidation of diacetyl-containing substrates with SeO₂ to the corresponding diglyoxals, followed by the reaction of these intermediates with o-phenylendiamine or 2,3-diaminonaphthalene, respectively. The basic optical and electrochemical properties of some 5,12-dihydroindolo[3,2-a]carbazoles were investigated.     

A convenient synthetic approach to dioncoquinone B and related compounds

A total synthesis of dioncoquinone B and related compounds, including ancistroquinones B, C and malvon A, is presented. The strategy is based on available reagents and can be used as a preparative synthesis of a number of natural and synthetic biologically active (3-alkyl)-2,7,8-di(tri)methoxy(hydroxy)-1,4-naphthoquinones.     

Domino Michael/aza-Wittig reaction in the diastereoselective construction of spiro[azepane-4,3′-oxindoles]

A convenient synthetic strategy for the diastereoselective assembly of spiro[azepane-4,3′-oxindoles] was developed via a Staudinger/Michael/aza-Wittig/reduction/N-deprotection reaction sequence starting from PMB-protected oxindole-substituted ethylazides. The key step of the method is a domino self-catalytic Michael/aza-Wittig reaction wherein the phosphazene moiety acts first as the catalyst and then as the reactant, resulting in the formation of a seven-membered N-heterocycle.     

Helicoidal Patterning of Nanorods with Polymer Ligands

Chiral packing of ligands on the surface of nanoparticles (NPs) is of fundamental and practical importance, as it determines how NPs interact with each other and with the molecular world. Herein, for gold nanorods (NRs) capped with end‐grafted nonchiral polymer ligands, we show a new mechanism of chiral surface patterning. Under poor solvency conditions, a smooth polymer layer segregates into helicoidally organized surface‐pinned micelles (patches). The helicoidal morphology is dictated by the polymer grafting density and the ratio of the polymer ligand length to nanorod radius. Outside this specific parameter space, a range of polymer surface structures was observed, including random, shish‐kebab, and hybrid patches, as well as a smooth polymer layer. We characterize polymer surface morphology by theoretical and experimental state diagrams. The helicoidally organized polymer patches on the NR surface can be used as a template for the helicoidal organization of other NPs, masked synthesis on the NR surface, as well as the exploration of new NP self‐assembly modes.     

Towards DNA Nanomachines for Cancer Treatment: Achieving Selective and Efficient Cleavage of Folded RNA

Despite decades of effort, gene therapy (GT) has failed to deliver clinically significant anticancer treatment, owing in part to low selectivity, low efficiency, and poor accessibility of folded RNA targets. Herein, we propose to solve these common problems of GT agents by using a DNA nanotechnology approach. We designed a deoxyribozyme‐based DNA machine that can i) recognize the sequence of a cancer biomarker with high selectivity, ii) tightly bind a structured fragment of a housekeeping gene mRNA, and iii) cleave it with efficiency greater than that of a traditional DZ‐based cleaving agent. An important advantage of the DNA nanomachine over other gene therapy approaches (antisense, siRNA, and CRISPR/cas) is its ability to cleave a housekeeping gene mRNA after being activated by a cancer marker RNA, which can potentially increase the efficiency of anticancer gene therapy. The DNA machine could become a prototype platform for a new type of anticancer GT agent.     

One-pot synthesis of quaternary pyridinium salts and tetrahydropyridine derivatives of fusidane triterpenoids

Chemistry of Heterocyclic Compounds - An efficient one-pot method was developed for the preparation of quaternary pyridinium salts and tetrahydropyridine derivatives of fusidane triterpenoids,...