Cationic Geminoid Peptide Amphiphiles Inhibit DENV2 Protease, Furin, and Viral Replication.

Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (CHC(O)-Lys-(Gly or Ala)Lys-NHCH, shorthand notation C-KXK-C with X = A or G, and = 0-2). The representatives with 1 or 2 Ala inhibit dengue protease and human furin, two serine proteases involved in dengue virus infection that have peptides with cationic amino acids as their preferred substrates, with IC values in the lower µM range.

Melting point prediction employing k-nearest neighbor algorithms and genetic parameter optimization.

We have applied the k-nearest neighbor (kNN) modeling technique to the prediction of melting points. A data set of 4119 diverse organic molecules (data set 1) and an additional set of 277 drugs (data set 2) were used to compare performance in different regions of chemical space, and we investigated the influence of the number of nearest neighbors using different types of molecular descriptors. To compute the prediction on the basis of the melting temperatures of the nearest neighbors, we used four different methods (arithmetic and geometric average, inverse distance weighting, and exponential weighting), of which the exponential weighting scheme yielded the best results.

Kinetics of biomarkers: biological and technical validity of isoprostanes in plasma.

Isoprostanes, non-enzymatic peroxidation products of arachidonic acid, are attractive biomarkers of oxidative stress in research in biology, medicine and nutrition. For the appropriate use of biomarkers it is required that these are both biologically and technically valid. Whereas the biological validity of isoprostanes is well-established, it is technically quite complicated to measure isoprostanes and its metabolites in body fluids, and its rapid disappearance from plasma may hamper practical application.

Expression screening, protein purification and NMR analysis of human protein domains for structural genomics.

Structural genomics, the determination of protein structures on a genome-wide scale, is still in its infancy for eukaryotes due to the number and size of their genes. Low protein expression and solubility of eukaryotic geneproducts are the major bottlenecks in high-throughput (HTP) recombinant protein production with the E. coli expression systems.

Global structure of a DNA three-way junction by solution NMR: towards prediction of 3H fold.

Three-way junctions (3H) are the simplest and most commonly occurring branched nucleic acids. They consist of three double helical arms (A to C), connected at the junction point, with or without a number of unpaired bases in one or more of the three different strands. Three-way junctions with two unpaired bases in one strand (3HS2) have a high tendency to adopt either of two alternative stacked conformations in which two of the three arms A, B and C are coaxially stacked, i.