Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A

Staphylococcus aureus (S. aureus) is a causative agent of many hospital- and community-acquired infections with the tendency to develop resistance to all known antibiotics. Therefore, the development of novel antistaphylococcal agents is of urgent need. Sortase A is considered a promising molecular target for the development of antistaphylococcal agents. The main aim of this study was to identify novel sortase A inhibitors. In order to find novel antistaphylococcal agents, we performed phenotypic screening of a library containing 15512 compounds against S. aureus ATCC43300. The molecular docking of hits was performed using the DOCK program and 10 compounds were selected for in vitro enzymatic activity inhibition assay. Two inhibitors were identified, N,N-diethyl-N′-(5-nitro-2-(quinazolin-2-yl)phenyl)propane-1,3-diamine (1) and acridin-9-yl-(1H-benzoimidazol-5-yl)-amine (2), which decrease sortase A activity with IC₅₀ values of 160.3 µM and 207.01 µM, respectively. It was found that compounds 1 and 2 possess antibacterial activity toward 29 tested multidrug resistant S. aureus strains with MIC values ranging from 78.12 to 312.5 mg/L. These compounds can be used for further structural optimization and biological research.     

The Acylpolyamines from the Venom of the Spider Agelenopsis aperta

The lyophilized venom of the spider Agelenopsis aperta (Aranea: Agelenidae) has been re‐analyzed by on‐line coupled high‐performance liquid chromatography and atmospheric‐pressure chemical‐ionization mass spectrometry (HPLC‐UV(DAD)‐APCI‐MS and MS/MS). Thus, 33 acylpolyamines with 11 different molecular masses, present in various concentrations, were detected, and their structures were disclosed. Different types of possible fragmentation as well as principles of structure elucidation are discussed. The method can be used for rapid separation and analysis of spider‐venom constituents.     

The maximum ratio clique problem

Computational Management Science - This paper introduces a fractional version of the classical maximum weight clique problem, the maximum ratio clique problem, which is to find a maximal clique...     

Interaction of the Iron(II) Cage Complexes With Proteins: Protein Fluorescence Quenching Study

Interaction of the iron(II) mono- and bis-clathrochelates with bovine serum albumin (BSA), β-lactoglobulin, lysozyme and insulin was studied by the steady-state and time-resolved fluorescent spectroscopies. These cage complexes do not make significant impact on fluorescent properties of β-lactoglobulin, lysozyme and insulin. At the same time, the monoclathrochelates strongly quench a fluorescence intensity of BSA and substantially decrease its excited state lifetime due to their binding to this protein. This occurs due to the excitation energy transfer from a tryptophan residue to a cage molecule or/and to the change of the tryptophan nearest environment caused by either clathrochelate binding or an alteration of the BSA conformation. The effect of the iron(II) bis-clathrochelate on BSA fluorescence is much weaker as compared to its monomacrobicyclic analogs as a result of an increase in its size.     

Structure/Property Relationships for Poly(Vinylidene Fluoride)/Doped Polyaniline Blends

Poly(vinylidene fluoride) (PVDF) and its blends with polyaniline (PANI) doped with dodecylbenzene sulfonic acid (DBSA) were characterized by electrical conductivity, differential scanning calorimetry (DSC) and X‐ray scattering techniques.

The onset of an infinite cluster (InC) of conducting, highly anisometric PANI/DBSA particles in PVDF/(PANI/DBSA) blends was observed at the percolation threshold as low as w*≈3.5 wt.%. The small angle X‐ray scattering (SAXS) data confirmed the expected spatial organization of PANI/DBSA needles into fractal‐like structures above w*. A slight decrease of both the DSC and the wide‐angle X‐ray scattering (WAXS) degrees of crystallinity of PVDF with the PANI/DBSA mass content w was explained by strong interactions at the PVDF/(PANI/DBSA) interface resulting in the loss of crystallizability of a fraction of sterically immobilized chains of PVDF in boundary layers around PANI/DBSA particles. The available data suggest that the conductive paths within InC of PANI/DBSA in PVDF/(PANI/DBSA) blends were formed primarily by the end‐to‐end contacts of PANI/DBSA fibrils.     

A coarse-grained model for β-<Emphasis Type="SmallCaps">d</Emphasis>-glucose based on force matching

Cellulosic ethanol production is a two-stage process that involves the hydrolysis of cellulose to form simple sugars and the fermentation of these sugars to ethanol. Hydrolysis of cellulose is the rate-limiting step, and there is a great need to characterize the process with numerical simulations to better understand the complex mechanisms involved. The ultimate goal is to generate accurate coarse-grained molecular models that are capable of predicting the structure of lignocellulose before and after pretreatment so that subsequent ab initio calculations can be performed to probe the degradation pathways. As a first step toward that goal, the force-matching method is used to derive coarse-grained models for β-d-glucose molecules in aqueous solution. Using the same reference, an all-atom molecular dynamics simulation trajectory, two sets of three- and six-site coarse-grained models of β-d-glucose are developed using two definitions of the coarse-grained center site location: center of mass (CG-CM) and geometric center (CG-GC). The performance of these coarse-grained models is evaluated by comparing the coarse-grained predictions for bond-length distributions and radial distribution functions to those obtained from the all-atom reference simulation. The six-site coarse-grained models retain more structural details than the three-site coarse-grained models. Comparison between center site definitions shows that CG-CM models generally predict local ordering better, while CG-GC models predict long-range structure better.