Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach

Abstract  

Antibiotics are chemotherapeutic agents with activity against microorganisms, for example bacteria, fungi, or protozoa, used for the treatment of many types of diseases. Binding of antibiotics to serum proteins in human plasma is a major determinant of their pharmacodynamic and pharmacokinetic behavior and, consequently, can affect their systemic distribution in the body. Here, the predicted binding rates of ceftazidime and 13 other pharmacological agents classified as antibiotics to plasma proteins (percentage fraction bound; PFB) were evaluated by use of 3D-QSAR models. We attempted to establish the contribution of hydrogen bond donor/acceptor and hydrophobic properties supplied by electrostatic fields to the PFB. Significant cross-validated correlation q ² (0.5–0.7) and the fitted correlation r ² (0.7–0.97) coefficients revealed that these models have reasonable power to predict the design 19 new antibiotics using ceftazidime as template, these compounds being our suggestion for further studies.     

Radiometric and fluorimetric determination of aminosilanes and protein covalently bound to thermally pretreated glass substrates

Derivatization of solid soda-lime glass spheres with aminosilanes and the stability of these groups near physiological pH in flow streams of aqueous buffered solutions are described. The presence of immobilized and adsorbed amines in the nanomolar range is confirmed by using two independent methods, one based on a radiotracer and the other on the fluorescent marker, fluorescamine. A method for covalently attaching bovine serum albumin to the beads is described.     

Two-dimensional electrophoresis of membrane proteins

One third of all genes of various organisms encode membrane proteins, emphasizing their crucial cellular role. However, due to their high hydrophobicity, membrane proteins demonstrate low solubility and a high tendency for aggregation. Indeed, conventional two-dimensional gel electrophoresis (2-DE), a powerful electrophoretic method for the separation of complex protein samples that applies isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in the second dimension, has a strong bias against membrane proteins. This review describes two-dimensional electrophoretic techniques that can be used to separate membrane proteins. Alternative methods for performing conventional 2-DE are highlighted; these involve replacing the IEF with electrophoresis using cationic detergents, namely 16-benzyldimethyl-n-hexadecylammonium chloride (16-BAC) and cetyl trimethyl ammonium bromide (CTAB), or the anionic detergent SDS. Finally, the separation of native membrane protein complexes through the application of blue and clear native gel electrophoresis (BN/CN-PAGE) is reviewed, as well as the free-flow electrophoresis (FFE) of membranes.     

Controlled delivery of proteins into bilayer lipid membranes on chip

The study and the exploitation of membrane proteins for drug screening applications requires a controllable and reliable method for their delivery into an artificial suspended membrane platform based on lab-on-a-chip technology. In this work, a polymeric device for forming lipid bilayers suitable for electrophysiology studies and biosensor applications is presented. The chip supports a single bilayer and is configured for controlled protein delivery through on-chip microfluidics. In order to demonstrate the principle of protein delivery, the potassium channel KcsA was reconstituted into proteoliposomes, which were then fused with the suspended bilayer on-chip. Fusion of single proteoliposomes with the membrane was identified electrically. Single channel conductance measurements of KcsA in the on-chip bilayer were recorded and these were compared to previously published data obtained with a conventional planar bilayer system.     

Growth and characterization of Mn- and Co-doped ZnO nanowires

A flow injection chemiluminescence method is proposed for the determination of cobalt, based on the strong catalytic effect of Cobalt(II) (1,10-phenanthroline)₃ complex on the lucigenin-periodate reaction in alkaline medium. Under the optimum experimental conditions, the chemiluminescence signal responded linearly to the concentration of cobalt(II) in the 1.0 × 10⁻⁹–3.0 × 10⁻⁷ g mL⁻¹ range with a detection limit of 4.4 × 10⁻¹⁰ g mL⁻¹ cobalt(II). The relative standard deviation for the determination of 5.0 × 10⁻⁸ g mL⁻¹ of cobalt was 2.3% in eleven replicated measurements. The method was successfully applied to the determination of cobalt(II) in pharmaceutical preparations.     

Chaotic synchronization of memristive neurons: Lyapunov function versus Hamilton function

Nonlinear Dynamics - In this paper, we consider a 5-dimensional Hindmarsh–Rose neuron model. This improved version of the original model shows rich dynamical behaviors, including a chaotic...     

Embedding polynomial matrices of one variable

A non square matrix with coefficients in K[z] can (if a condition on its minors is satisfied) be embedded into a square matrix with determinant 1. Finding theoretically and in an algorithmic way an embedding of small degree is solved by a construction with vector bundles on the projective line over K.     

Four applications of majorization to convexity in the calculus of variations

The resemblance between the Horn-Thompson theorem and a recent theorem by Dacorogna-Marcellini-Tanteri indicates that Schur-convexity and the majorization relation are relevant for applications in the calculus of variations and its related notions of convexity, such as rank one convexity or quasiconvexity. In Theorem 6.6, we give simple necessary and sufficient conditions for an isotropic objective function to be rank one convex on the set of matrices with positive determinant.Majorization is used in order to give a very short proof of a theorem of Thompson and Freede [R.C. Thompson, L.J. Freede, Eigenvalues of sums of Hermitian matrices III, J. Res. Nat. Bur. Standards B 75B (1971) 115-120], Ball [J.M. Ball, Constitutive inequalities and existence theorems in nonlinear elastostatics, in: R.J. Knops (Ed.), Nonlinear Analysis and Mechanics: Heriot-Watt Symposium, vol. 1, Res. Notes Math., 17, Pitman, 1977, pp. 187-241], or Le Dret [H. Le Dret, Sur les fonctions de matrices convexes et isotropes, CR Acad. Sci. Paris, Série I 310 (1990) 617-620], concerning the convexity of a class of isotropic functions which appear in nonlinear elasticity.Next we prove (Theorem 7.3) a lower semicontinuity result for functionals with the form _∫Ωw(D?(x))dx, with w(F)=h(lnV_F). Here F=R_FU_F=V_FR_F is the usual polar decomposition of F∈gl(n,R), and lnV_F is Hencky’s logarithmic strain.We close this paper with a compact proof of Dacorogna-Marcellini-Tanteri theorem, based only on classical results about majorization. The mentioned resemblance of this theorem with the Horn-Thompson theorem is thus explained.     

W(bipy)(CN)6]-: a suitable metalloligand in the design of heterotrimetallic complexes. The first Cu(II)Ln(III)W(V) trinuclear complexes

The first 3d-4f-5d heterotrimetallic complexes using [W(V)(bipy)(CN)(6)](-) as a metalloligand were synthesized (bipy = 2,2'-bipyridine). The structural and magnetic properties of three [Cu(II)Ln(III)W(V)] complexes (Ln = Gd, Ho, Tb) are discussed.