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Synthetic immunostimulants (excluding sulfur-containing compounds).

Many different approaches have been used, over the last 15 years, for the design of potential immunostimulating drugs: Fractionation of crude natural substances (of eukaryotic or prokaryotic origin) already known to enhance immune functions, followed by chemical characterization and, in many cases, full synthesis of the active moiety: examples are provided by thymic hormones and the muramyldipeptide (MDP); Chemical modification of natural substances of known chemical structure in order to potentiate or change their biological activities or reduce their toxicity: murabutide, lipophilic MDP derivatives, lipopeptides (such as pimelautide), tuftsin analogs; Chemical synthesis (often without preconceived ideas about structure-activity relationship) of a great variety of molecules which are then screened in vitro and in vivo for immunopharmacological activity. The chemical structures and the biological profiles (in terms of possible primary cellular targets and mechanisms of immunostimulating activities) of representatives of class (b) and class (c) immunostimulants are reviewed in this paper.

Acetylmuramyl-Alanyl-Isoglutamine↗

Sulfur K-edge X-ray absorption spectroscopy for determining the chemical speciation of sulfur in biological systems.

Sulfur is an essential biological element, yet its biochemistry is only partially understood because there are so few tools for studying this element in biological systems. X-ray absorption spectroscopy provides a unique approach to determining the chemical speciation of sulfur in intact biological samples. Different biologically relevant sulfur compounds show distinctly different sulfur K-edge X-ray absorption spectra, and we show here, as an example, that this allows the deconvolution of the sulfur species in equine blood.

Absorptiometry, Photon↗

Oxygen-containing sulfur-rich compounds from the bark of the tropical garlic tree Scorodophloeus zenkeri Harms.

Two sulphoxides (2,3,5-trithiahexane 5-oxide and 2,4,5,7-tetrathiaoctane 2-oxide), three novel sulphones [S-(methylthiomethyl)methanesulfonothioate, methylthio(methylthio-methyl)sulfone, 2,3,5,7-tetrathiaoctane3,3-dioxide] and four known sulphones [methylsulphonylmethylthiomethane, methylmethanethiosulfonate, bis-methyl-sulphonylmethane, and bis-(methylthiomethyl)sulfone] were isolated from the bark extracts of Scorodophloeus zenkeri Harms. The structures were determined by spectral methods, essentially MS and NMR experiments.

Caesalpinia↗

A novel gene encoding a sulfur-regulated outer membrane protein in Thiobacillus ferrooxidans.

Thiobacillus ferrooxidans is a Gram-negative chemolithotrophic bacterium able to oxidize ferrous iron, elemental sulfur and inorganic sulfur compounds. The oxidation of sulfur by T. ferrooxidans resulted in an expression of some outer membrane proteins (OMPs) at a level higher than that observed during ferrous iron oxidation. Among these OMPs, a protein with a molecular mass of 54 kDa was purified and 18 amino acids of the N-terminal sequence determined. Using a 54 bp PCR generated DNA product as a probe for the protein, we isolated a 4.5 kb Pst I DNA chromosomal fragment containing the corresponding gene. Sequencing 2169 bp of this fragment revealed the open reading frame codifying for the protein, consisting of 467 amino acids and a molecular mass of 49,674 Da. The mature protein was produced by the removal of a 32 amino acid signal peptide-like sequence from the N-terminus of a 499 amino acid peptide. Although no significant homology with any known protein has been found and its physiological role remains unclear, its high expression on sulfur substrates suggests a role in sulfide mineral oxidation.

Amino Acid Sequence↗