High confidence prediction of essential genes in burkholderia cenocepacia

Essential genes are absolutely required for the survival of an organism. The identification of essential genes, besides being one of the most fundamental questions in biology, is also of interest for the emerging science of synthetic biology and for the development of novel antimicrobials. New antimicrobial therapies are desperately needed to treat multidrug-resistant pathogens, such as members of the Burkholderia cepacia complex.

Malondialdehyde scavenging and aldose-derived Schiff bases' transglycation properties of synthetic histidyl-hydrazide carnosine analogs.

Second-generation carnosine analogs bearing the histidyl-hydrazide moiety have been synthesized and tested for their efficiency in scavenging malondialdehyde (MDA) derived from lipid peroxidation and for their ability to reverse the glycation process in the glucose-ethylamine Schiff base model. The data obtained indicate that this class of compounds maintains the activity profile of carnosine and is a suitable candidate for the treatment of disorders caused by oxidative stress.

Cyclic AMP production and insulin releasing activity of synthetic fragment peptides of glucose-dependent insulinotropic polypeptide

Synthetic fragment peptides of glucose-dependent insulinotropic polypeptide (GIP) were evaluated for their ability to elevate cellular cAMP production and stimulate insulin secretion. In GIP receptor transfected CHL cells, GIP(4-42) and GIP(17-30) dose-dependently inhibited GIP-stimulated cAMP production (40 +/- 8%; p <0.01 and 15 +/- 6%; p <0.05, respectively), while GIP(1-16) exerted very weak agonist effects on cAMP production. In the clonal pancreatic beta-cell line, BRIN-BD11, GIP(1-16) demonstrated weak insulin releasing activity compared with native GIP. In contrast, GIP(4-42) and GIP (17-30) weakly antagonized the insulin releasing activity of the native peptide (23 +/- 6%; p <0.05 and 11 +/- 3%, respectively). These data demonstrate the critical role of the N-terminus and the involvement of regions of the C-terminal domain in generating full biological potency of GIP.

Antimicrobial activity of short, synthetic cationic lipopeptides.

The increasing emergence of multidrug-resistant micro-organisms presents one of the greatest challenges in the clinical management of infectious diseases. Therefore, novel antimicrobial agents are urgently required to address this issue. In this report, we describe the solid phase synthesis, characterization, microbiological and toxicological evaluation of a library of ultrashort cationic antimicrobial lipopeptides based on the previously described tetrapeptide amide H-Orn-Orn-Trp-Trp-NH2 conjugated with saturated fatty acids which have inherent antimicrobial activity. The microbiological activity of these ultrashort cationic lipopeptides, which exhibit excellent, broad-spectrum antimicrobial activity against a number of clinically important pathogenic bacteria and fungi, including multidrug resistant micro-organisms in both planktonic and sessile (biofilm) cultures is reported.

Rapid confirmatory method for the determination of sixteen synthetic growth promoters and bisphenol A in bovine milk using dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry

A rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-residue method for the simultaneous quantitation and identification of sixteen synthetic growth promoters and bisphenol A in bovine milk has been developed and validated. Sample preparation was straightforward, efficient and economically advantageous. Milk was extracted with acetonitrile followed by phase separation with NaCl. After centrifugation, the extract was purified by dispersive solid-phase extraction with C18 sorbent material. The compounds were analysed by reversed-phase LC-MS/MS using both positive and negative ionization and operated in multiple reaction monitoring (MRM) mode, acquiring two diagnostic product ions from each of the chosen precursor ions for unambiguous confirmation. Total chromatographic run time was less than 10 min for each sample. The method was validated at a level of 1 mu g L-1. A wide variety of deuterated internal standards were used to improve method performance. The accuracy and precision of the method were satisfactory for all analytes. The confirmative quantitative liquid chromatographic tandem mass spectrometric (LC-MS/MS) method was validated according to Commission Decision 2002/657/EC. The decision limit (CC alpha) and the detection capability (CC beta) were found to be below the chosen validation level of 1 mu g L-1 for all compounds. (C) 2010 Elsevier B.V. All rights reserved.

Novel synthetic route to the C-nucleoside, 2-deoxy benzamide riboside

2-Deoxy-C-nucleosides are a subcategory of C-nucleosides that has not been explored extensively, largely because the synthesis is less facile. Flexible synthetic procedures giving access to 2-deoxy-C-nucleosides are therefore of interest. To exemplify the versatility and highlight the limitations of a synthetic route recently developed to that effect, the first synthesis of 2-deoxy benzamide riboside is reported. Biological properties of this novel C-nucleoside are also discussed. (c) 2012 Elsevier Ltd. All rights reserved.

Feleucin-BO1: A Novel Antimicrobial Non-Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad-Spectrum Synthetic Analogue, Feleucin-K3

Feleucins-BV1 and -BV2 are recently-described prototypes of a novel antimicrobial nonapeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μM) but was inactive (> 250 μM) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly-enhanced potency and spectrum of activity. The MICs of F-K3 against the reference microorganisms were 7 μM (S. aureus), 14 μM (E. coli) and 7 μM (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.