Cyclodextrin knowledgebase a web-based service managing CD-ligand complexation data

Cyclodextrins are cyclic oligosaccharides that are able to form water-soluble inclusion complexes with small molecules. Because of their complexing ability, they are widely applied in food, pharmaceutical and chemical industries. In this paper we describe the development of a free web-service, Cyclodextrin KnowledgeBase: (http://www.cyclodextrin.net). The database contains four modules: the Publication, Interaction, Chirality and Analysis Modules. In the Publication Module, almost 50,000 publication details are collected that can be retrieved by text search. In the Interaction and Chirality Modules relevant literature data on cyclodextrin complexation and chiral recognition are collected that can be retrieved by both text and structural searches. Moreover, in the Analysis Module, the geometries of small molecule-cyclodextrin complexes can be predicted using molecular docking tools in order to explore the structures and interaction energies of the inclusion complexes. Complex geometry prediction is made possible by the built-in database of 95 cyclodextrin derivatives, where the 3D structures as well as the partial charges are calculated and stored for further utilization. The use of the database is demonstrated by several examples.     

A generalization of the Discrete Isoperimetric Inequality for Piecewise Smooth Curves of Constant Geodesic Curvature

Summary The discrete isoperimetric problem is to determine the maximal area polygon with at most <InlineEquation ID=IE"1"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"2"><EquationSource Format="TEX"><![CDATA[$]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>k$ vertices and of a given perimeter. It is a classical fact that the unique optimal polygon on the Euclidean plane is the regular one. The same statement for the hyperbolic plane was proved by K\'aroly Bezdek [1] and on the sphere by L\'aszl\'o Fejes T\'oth [3]. In the present paper we extend the discrete isoperimetric inequality for ``polygons' on the three planes of constant curvature bounded by arcs of a given constant geodesic curvature.     

On the Lipschitz perturbation of monotonic functions

Summary A real valued function <InlineEquation ID=IE"5"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"6"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"7"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"8"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"9"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"10"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"11"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"12"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"13"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"14"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"15"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"16"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"17"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"18"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"19"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"20"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"21"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"22"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"23"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"24"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"25"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"26"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"27"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"28"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"29"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"30"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"31"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"32"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"33"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"34"><EquationSource Format="TEX"><![CDATA[$]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>f$ defined on a real interval $I$ is called \emph{$d$-Lipschitz} if it satisfies $|\ell(x)- \ell(y)| \le d(x,y)$ for $x,y\in I$. In this paper, we investigate when a function $p\: I \to \bR$ can be decomposed in the form $p=q+ \ell$, where $q$ is increasing and $\ell$ is $d$-Lipschitz. In the general case when $d\: I^{2} \to \bR$ is an arbitrary semimetric, a function $p\: I \to \bR$ can be written in the form $p=q+ \ell$ if and only if \vspace{-4pt} <InlineEquation ID=IE"1"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"2"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"3"><EquationSource Format="TEX"><![CDATA[<InlineEquation ID=IE"4"><EquationSource Format="TEX"><![CDATA[$$]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation>]]></EquationSource></InlineEquation> \sum_{i=1}^{n}{\big(p(s_{i})-p(t_{i})-d(t_{i},s_{i}) \big)^{+}} \le \sum_{j=1}^{m}{\big(p(v_{j})-p(u_{j})+d(u_{j},v_{j}) \big)} \vspace{-4pt} $$ is fulfilled for all real numbers $t_{1}<s_{1}, \dots, t_{n}<s_{n}$ and $u_{1}<v_{1}, \dots, u_{m}<v_{m}$ in $I$ satisfying the condition \vspace{-4pt} $$ \sum_{i=1}^{n} 1_{\left]t_i,s_i\right]}= \sum_{j=1}^{m} 1_{\left]u_j,v_j\right]}, \vspace{-4pt} $$ where $1_{\left]a,b\right]}$ denotes the characteristic function of the interval $\left]a,b\right]$. In the particular case when $d\: I^{2} \to R$ is a so-called concave semimetric, a function $p\: I \to \bR$ is of the form $p=q+ \ell$ if and only if \vspace{-4pt} $$ 0 \le \sum_{k=1}^{n}{d(x_{2k-1},x_{2k})} + d(x_0,x_{2n+1}) + \sum_{k=0}^{n}{\big(p(x_{2k+1})-p(x_{2k})\big)} \vspace{-4pt} $$ holds for all $x_0\le x_1\ki \cdots\ki x_{2n}\le x_{2n+1}$ in $I$.     

Comparative analysis of binding energy of chymostatin with human cathepsin A and its homologous proteins by molecular orbital calculation

Cathepsin A is a mammalian lysosomal enzyme that catalyzes the hydrolysis of the carboxy-terminal amino acids of polypeptides and also regulates beta-galactosidase and neuraminidase-1 activities through the formation of a multienzymic complex in lysosomes. Human cathepsin A (hCathA), yeast carboxypeptidase (CPY), and wheat carboxypeptidase II (CPW) belong to the alpha/beta-hydrolase fold family. They have structurally similar active-site clefts, but there are small differences in the amino acid residues comprising their active sites that might determine the substrate specificity and sensitivity to microbial inhibitors including chymostatin. To examine the selectivity and binding mechanism of chymostatin as to hCathA, CPY, and CPW at the atomic level, we analyzed the interaction energy between chymostatin and each protein quantitatively by semiempirical molecular orbital calculation AM1 with the continuum solvent model. We predicted the electrostatic repulsion between the P3 cyclic arginine residue of the inhibitor and the Arg344 in the S3 active subsite of hCathA. Genetic conversion of Arg344 of the wild-type hCathA to Ile also caused an increase in its sensitivity to chymostatin, which was correlated with the decrease in the interaction energy calculated with the molecular orbital method. The present results suggest that such molecular calculation should be useful for evaluating the interactions between ligands, including inhibitors and homologous enzymes, in their docking models.     

C‐perfect hypergraphs

Let ${\mathcal{H}}=({{X}},{\mathcal{E}})Let ${\mathcal{H}}=({{X}},{\mathcal{E}})$ be a hypergraph with vertex set X and edge set ${\mathcal{E}}$. A C‐coloring of ${\mathcal{H}}$ is a mapping ?:X→? such that |?(E)|<|E| holds for all edges ${{E}}\in{\mathcal{E}}$ (i.e. no edge is multicolored). We denote by $\bar{\chi}({\mathcal{H}})$ the maximum number |?(X)| of colors in a C‐coloring. Let further $\alpha({\mathcal{H}})$ denote the largest cardinality of a vertex set S?X that contains no ${{E}}\in{\mathcal{E}}$, and $\tau({\mathcal{H}})=|{{X}}|-\alpha({\mathcal{H}})$ the minimum cardinality of a vertex set meeting all $E \in {\mathcal{E}}$. The hypergraph ${\mathcal{H}}$ is called C‐perfect if $\bar{\chi}({\mathcal{H}}\prime)=\alpha({\mathcal{H}}\prime)$ holds for every induced subhypergraph ${\mathcal{H}}\prime\subseteq{\mathcal{H}}$. If ${\mathcal{H}}$ is not C‐perfect but all of its proper induced subhypergraphs are, then we say that it is minimally C‐imperfect. We prove that for all r, k∈? there exists a finite upper bound h(r, k) on the number of minimally C‐imperfect hypergraphs ${\mathcal{H}}$ with $\tau({\mathcal{H}})\le {{k}}$ and without edges of more than r vertices. We give a characterization of minimally C‐imperfect hypergraphs that have τ=2, which also characterizes implicitly the C‐perfect ones with τ=2. From this result we derive an infinite family of new constructions that are minimally C‐imperfect. A characterization of minimally C‐imperfect circular hypergraphs is presented, too. © 2009 Wiley Periodicals, Inc. J Graph Theory 64: 132–149, 2010     

A synthetic and in silico study on the highly regioselective Diels-Alder reaction of the polyenic antifungal antibiotics natamycin and flavofungin

The tetraenic macrolide antibiotic natamycin and the pentaenic macrolide flavofungin gave monoadducts on Diels-Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione. The regioselectivity of the reaction as well as the conformation of the products was studied using theoretical calculations.     

Nano-hydroxyapatite preparation from biogenic raw materials

Hydroxyapatite (HAp) was successfully produced from recycled eggshell, seashell and phosphoric acid. The phases obtained depended on the ratio of calcined eggshell/ seashell to phosphoric acid, the calcination temperature and the mechanochemical activation method (ball milling or attrition milling). The HAp structures were characterized by X-ray diffraction, scanning electron microsopy and infrared spectroscopy. Attrition milling was more effective than ball milling, yielding nanosize, homogenous and pure Hap.      

High-performance liquid chromatographic enantioseparation of monoterpene-based 2-amino carboxylic acids on macrocyclic glycopeptide-based phases

The enantiomers of five monoterpene-based 2-amino carboxylic acids were directly separated on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec Chirobiotic T and T2) and teicoplanin aglycone (Chirobiotic TAG) as chiral selectors. The effects of pH, the mobile phase composition, the structure of the analyte and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range 10–40 °C to study the effects of temperature and thermodynamic parameters on separations. Apparent thermodynamic parameters and T_iso values were calculated from plots of ln k or ln α versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantioseparations were in most cases enthalpy driven. The sequence of elution of the enantiomers was determined in all cases.     

Determination of rare-earth elements in uranium-bearing materials by inductively coupled plasma mass spectrometry

A novel and simple analytical procedure has been developed for the trace-level determination of lanthanides (rare-earth elements) in uranium-bearing materials by inductively coupled plasma sector-field mass spectrometry (ICP-SFMS). The method involves a selective extraction chromatographic separation of lanthanides using TRU™ resin followed by ICP-SFMS analysis. The limits of detection of the method proposed is in the low pg g⁻¹ range, which are approximately two orders of magnitude better than that of without chemical separation. The method was validated by the measurement of reference material and applied for the analysis of uranium ore concentrates (yellow cakes) for nuclear forensic purposes, as a potential application of the methodology.     

Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues

The mimicry of protein‐sized β‐sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin‐14 β‐sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β‐Residues with diverse structural properties were utilized: Homologous β³‐amino acids, (1R,2S)‐2‐aminocyclopentanecarboxylic acid (ACPC), (1R,2S)‐2‐aminocyclohexanecarboxylic acid (ACHC), (1R,2S)‐2‐aminocyclohex‐3‐enecarboxylic acid (ACEC), and (1S,2S,3R,5S)‐2‐amino‐6,6‐dimethylbicyclo[3.1.1]heptane‐3‐carboxylic acid (ABHC). Six α/β‐peptidic chains were constructed in both monomeric and disulfide‐linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β‐sheet formation in the 64‐residue foldameric systems. Core replacement with (1R,2S)‐ACHC was found to be unique among the β‐amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen‐bonding network and to fit sterically into the hydrophobic interior of the β‐sandwich. The novel β‐sandwich model containing 25 % unnatural building blocks afforded protein‐like thermal denaturation behavior.