Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.     

An effective multipurpose building block for 3D electropolymerisation: 2,2′-Bis(2,2′-bithiophene-5-yl)-3,3′-bithianaphthene

Novel thiophene-based oligomer, 2,2′-bis(2,2′-bithiophene-5-yl)-3,3′-bithianaphthene (TX), was designed and synthesized, and its electrochemical and spectral properties characterised. TX was readily polymerised electrochemically to form well organized conducting homopolymer films on various solid electrode substrates. Moreover, it was successfully used for deposition by electropolymerisation of electrochemically active thin films of co-polymers with three different monomers of functionalised bis(2,2′-bithienyl)methane derivatives. It appeared that TX was an effective crosslinker and 3D promoter in these electropolymerisations involving co-monomers intrinsically showing limited aptitude for the electropolymerisation or forming polymer films of low conductivity. This attractive TX ability stems from combination of its (i) high conjugation efficiency in each of the two planar moieties, (ii) intrinsic 3D structure on account of the presence of the central node, and (iii) intrinsic regioselectivity in electropolymerisation on account of the positions of the two available free α-thiophene sites.     

Modulation on C‐ and N‐Terminal Moieties of a Series of Potent and Selective Linear Tachykinin NK2 Receptor Antagonists

Herein we describe the synthesis of a series of new potent tachykinin NK₂ receptor antagonists by the modulation of the C‐ and N‐terminal moieties of ibodutant (MEN 15596, 1 ). The N‐terminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C‐terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK₂ receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK₂ receptor. Selected compounds were tested in vivo confirming their activity as NK₂ antagonists. In particular, after both iv and id administration to guinea pig, compound 61 b was able to antagonize NK₂‐induced colonic contractions with a potency and duration‐of‐action fully comparable to the reference compound 1 (MEN 15596, ibodutant).     

UNICORE 6 — Recent and Future Advancements

UNICORE is a European Grid Technology with more than 10 years of history. Originating from the Supercomputing domain, the latest version UNICORE 6 has turned into a general-purpose Grid technology that follows established standards and offers a rich set of features to its users. The paper starts with an architectural insight into UNICORE 6, highlighting the workflow features, standards and the different clients. Next, the current state of advancement is presented by describing recent developments. The paper closes with an outlook on future planned developments.     

Confirmation of brand identity in foods by near infrared transflectance spectroscopy using classification and class-modelling chemometric techniques — The example of a Belgian beer

Food and beverage processors require tools to monitor conformance of finished goods to their defined specification; regulatory authorities need appropriate methods for detecting retail fraud. In this report, samples (n = 275) of Belgian and other European beers were collected and analysed using near infrared transflectance spectroscopy; three class-modelling techniques (soft independent modelling of class analogy, SIMCA; potential functions techniques, POTFUN; and unequal dispersed classes, UNEQ) were employed to characterise beer types (firstly Trappist and then Rochefort) while a classification method (partial least squares discriminant analysis, PLS-DA) was applied to discriminate between two final beer classes: Rochefort 8° and Rochefort 10°. The class-models and the classification rules developed were validated by means of an external prediction set. A discussion on the appropriate use of these chemometric approaches is included. Modelling of Trappist beers met with limited success while model efficiencies for Rochefort samples were highest for SIMCA and UNEQ applications i.e. 81.4% and 84.5% respectively. The classification of beers as Rochefort 8? or Rochefort 10? was possible with an average correct classification rate of 93.4%.     

Plasmonic bandgap in random media

We present a dispersion theory of the surface plasmon polaritons (SPP) in random metal-dielectric nanocomposite (MDN) consisting of bulk metal embedded with dielectric inclusions. We demonstrate that embedding of dielectric nanoparticles in metal results in the formation of the plasmonic bandgap due to strong coupling of the SPP at the metal-vacuum interface and surface plasmons localized at the surface of nanoinclusions. Our results show that MDN can replace metals in various plasmonic devices, which properties can be tuned in a wide spectral range. Being compatible with waveguides and other photonic structures, MDN offers high flexibility in the plasmonic system design.