Chemical synthesis and biological evaluation of gallidermin-siderophore conjugates

The lantibiotic gallidermin was modified at lysine residues by regioselective attachment of derivatives of pyochelin, agrobactin and desferrioxamine B with the objective of having siderophore receptors of Gram-negative bacteria transport the antibiotic-iron chelator conjugate through the outer membrane. All of the conjugates retained activity against the Gram-positive indicator strain, Lactococcus lactis subsp. cremoris HP. However, testing of the conjugates against several Gram-negative strains yielded unexpected results. Bacteria treated with 100 μM of the conjugates complexed with Fe(3+) grew better than bacteria grown in iron-free media but worse than bacteria grown in the same media supplemented with 10 μM FeCl(3). Although these findings indicate that the conjugates are unable to inhibit the growth of Gram-negative bacteria, they indicate penetration of the outer membrane and provide structure-activity information for design of other lantibiotic conjugates. The synthetic strategy is applicable for linking biomarkers or fluorescence probes to gallidermin for studies on its localization and mode of action. As there are many lantibiotics that operate with unknown mechanisms of action, this chemical approach provides a means to modify such peptides with biomarkers for biological investigations.     

Dehalogenation of α -haloketones and vic-dibromides with nickel boride

α-Haloketones and $\text{vic}$-dibromides are converted to the corresponding ketones and alkenes respectively with nickel boride generated $\text{in situ}$ from sodium borohydride and nickel chloride.     

Relaxation phenomena of polar non-polar liquid mixtures under low and high frequency electric field

Simultaneous calculation of the dipole moment μ_j and the relaxation time τ_j of a certain number of non-spherical rigid aliphatic polar liquid molecules (j) in non-polar solvents (i) under 9.8 GHz electric field is possible from real ε′_ij and imaginary ε″_ij parts of the complex relative permittivity ε*_ij. The low frequency and infinite frequency permittivities ε_0ij and ε_∞ij measured by Purohitet al [1,2] and Srivastava and Srivastava [3] at 25, 35 and 30°C respectively are used to obtain static μ_s. The ratio of the individual slopes of imaginary σ″_ij and real σ′_ij parts of high frequency (hf) complex conductivity σ*_ij with weight fractionsw _jatw _j → 0 and the slopes of σ″_ij— σ′_ij curves for differentw _js [4] are employed to obtain τ_js. The former method is better in comparison to the existing one as it eliminates polar-polar interaction. The hf μ_js in Coulomb metre (C m) when compared with static and reported μs indicate that μ_s s favour the monomer formations which combine to form dimers in the hf electric field. The comparison among μs shows that a part of the molecule is rotating under X-band electric field [5]. The theoretical μ_theos from available bond angles and bond moments of the substituent polar groups attached to the parent molecules differ from the measured μ_js and μs to establish the possible existence of mesomeric, inductive and electromeric effects in polar liquid molecules.     

A preparation of bromoolefins from carbonyl compounds

A variety of 1-bromoalkenes are prepared by addition of dibromomethyllithium to ketones and aldehydes followed by reductive elimination with zinc-acetic acid. The product E/Z ratios were determined, and halogen-lithium exchange with t-butyllithium was examined.     

Molecular views and measurements of hemostatic processes using atomic force microscopy

Hemostasis and thrombosis are highly complex and coordinated interfacial responses to vascular injury. In recent years, atomic force microscopy (AFM) has proven to be a very useful approach for studying hemostatic processes under near physiologic conditions. In this report, we review recent progress in the use of AFM for studying hemostatic processes, including molecular level visualization of plasma proteins, protein aggregation and multimer assembly, and structural and morphological details of vascular cells under aqueous conditions. AFM offers opportunities for visualizing surface-dependent molecular and cellular interactions in three dimensions on a nanoscale and for sensitive, picoNewton level, measurements of intermolecular forces. AFM has been used to obtain molecular and sub-molecular, resolution of many biological molecules and assemblies, including coagulation proteins and cell surfaces. Surface-dependent molecular processes including protein adsorption, conformational changes, and subsequent interactions with cellular components have been described. This review outlines the basic principles and utility of AFM for imaging and force measurements, and offers objective perspectives on both the advantages and disadvantages. We focus primarily on molecular level events related to hemostasis and thrombosis, particularly coagulation proteins, and blood platelets, but also explore the use of AFM in force measurements and surface property mapping.