The N-acetylneuraminic acid content of five forms of human transferrin

Five isoforms of human serum transferrin were separated by isoelectric focusing and their N-acetylneuraminic acid content was determined. The forms differed in isoelectric point by about 0.1 of a pH unit with the structural differences situated in the carbohydrate parts. Each form had one sialic acid molecule (NANA) less than the next most acidic form. GLC-MS showed that the most abundant form with isoelectric point 5.5 had two two-branched carbohydrate chains, each having the galactoses covered by terminal sialic acid. The form with isoelectric point 5.4 had one three-branched and one two-branched carbohydrate chain, and all branches terminated with a sialic acid residue. The form with isoelectric point 5.6 had a terminal galactose on one of its two two-branched carbohydrate chains. Comparison of the sialic acid content of the five transferrin forms and their carbohydrate structures showed that some of the forms expose terminal galactose without attracting the asialoglycoprotein receptors on hepatocytes.     

Amino acid preferences of small, naturally occurring polypeptides

An analysis of amino acid composition of small, naturally occurring peptides ranging in size from 3 to 50 residues has been carried out. The purpose of the study is to determine whether differential trends in amino acid usage exist for small peptides compared to larger polypeptides and proteins. Results indicate that Cys, Trp, and Phe are substantially more frequent in peptides compared to their abundance in proteins at large. Aliphatic hydrophobic residues, particularly Leu and Ile, are somewhat underrepresented, while the frequency of Glu is significantly reduced. The shorter peptides are also more frequently neutral and become increasingly charged as their size increases.     

Tetraoxygenated naturally occurring xanthones

This review, with 350 references, gives information on the chemical study of 234 naturally occurring tetraoxygenated xanthones in 12 families, 53 genus and 182 species of higher plants, and two which are described as fungal and lichen metabolites. The value of these groups of substances in connection with pharmacological activity and therapeutic use of some species is described. The structural formulas of 135 isolated compounds, and their distribution, are also given.     

Genotoxicity of naturally occurring hydroxyanthraquinones

A variety of structurally related hydroxyanthraquinones (HA) were investigated in a test battery for the evaluation of mutagenicity and cell-transforming activity. The tests were: (1) the Salmonella typhimurium mutagenicity assay, (2) the V79-HGPRT mutagenicity assay, (3) the DNA-repair induction assay in primary rat hepatocytes and (4) the in vitro transformation of C3H/M2 mouse fibroblasts. In Salmonella, most of the tested compounds were mutagenic in strain TA1537, but only a few were active in other strains. Among these were HA with a hydroxymethyl group, such as lucidin and aloe-emodin. In V79 cells, only HA with 2 hydroxy groups in the 1,3 positions (1,3-DHA, purpurin, emodin) or with a hydroxymethyl sidechain (lucidin and aloe-emodin) were mutagenic. The compounds found to be active in V79 cells were also active in the DNA-repair assay and in the C3H/M2 transformation assay. Thus, it appears that the genotoxicity of HA is dependent on certain structural requirements.     

Radioiodination of naturally occurring phospholipids

A simple and rapid nonenzymatic method for radioiodination of phospholipids is described. It involves oxidation of Na125I with TlCl3 (or chloramine-T) in an aqueous medium, with subsequent exposure of the phospholipids, dissolved in chloroform/methanol, to the action of the oxidizing mixture. Purification of the radiolabelled phospholipids was effected by washing with sodium thiosulphate followed by thin-layer chromatography on silica gel. Specific radioactivity of 125I-labelled phosphatidylcholine was estimated to be about 10 muCi/mg phospholipid. The method is designed for radioiodination of various naturally occurring phospholipids.     

Evidence for naturally occurring hyaluronic acid binding protein in rat liver

Hyaluronic acid binding protein (HBP) was purified homogeneously from normal adult rat liver by hyaluronate-sepharose affinity chromatography. The molecular weight of this protein as determined by gel filtration was found to be 64,000 daltons. This protein HBP appeared as a single band in non-dissociating gel electrophoresis and has a subunit of molecular weight approximately 12,000 as determined by SDS-gel electrophoresis.     

Lipase-catalyzed acetylation of N-acetylneuraminic acid derivative

A facile preparation of triacetylated derivative of 2-phenylthioglycoside of N-acetylneuraminic acid (4) was achieved by treatment with lipase PS in vinyl acetate. The major product 4 has a free hydroxyl group at C-7. Results of time-course HPLC analysis indicate that the reactivity of the hydroxyl groups under this condition is in the following order; C-9 > C-4 > C-8 > C-7.     

Multiple forms of metallothionein from the digestive gland of naturally occurring and cadmium-exposed mussels, Mytilus galloprovincialis

Polymorphism of metallothioneins in the digestive gland of naturally occurring (control) and experimentally Cd-exposed mussels Mytilus galloprovincialis (200 μg Cd l^–1; 14 days) was studied by applying the conventional methods of Sephadex column liquid chromatography (G-75 and DEAE A-25), and by an electrochemical method (DPASV) for determination of Cd, Zn and Cu concentrations in chromatographic fractions. In both control and Cd-exposed mussels, two distinct molecular mass components of the metallothioneins, monomeric (MT-10) and dimeric (MT-20), were resolved by Sephadex G-75 gel filtration chromatography. In control mussels, the MT-10 component was predominantly expressed as containing markedly higher constitutive levels of Zn (100×) and Cu (10×) than of Cd. Each of these two molecular mass components was further resolved into seven metal-rich peaks by anion-exchange chromatography. In Cd-exposed mussels the larger proportion of Cd was bound to the MT-20 than to the MT-10 component, suggesting that the dimeric component may be considered as a primarily inducible metallothionein. The elution positions of metal-binding maxima of Cd-exposed and control mussels on the respective DEAE chromatographic profiles were comparable. A great similarity in elution positions of Cd maxima between the composite and single-specimen samples was also observed. Our study confirms a high multiplicity of MT forms in mussels from the Mytilus genus not only under the laboratory high-level metal exposure conditions, but also at a natural seawater metal exposure level. The ecotoxicological significance of dimeric and monomeric MT forms, as well as their possible application in the biomonitoring of seawater for trace metals, has been considered. Electronic Publication     

The effect of synthetic and naturally occurring trehalose fatty acid esters in tumor regression

Summary Dimycolates of trehalose, purified cord factor (P3), or monomycolates of trehalose (P4) isolated from various species of mycobacteria, when emulsified with oil droplets and endotoxins from 0 antigen-deficient Re mutants of Salmonella typhimurium or S. minnesota, were found to be effective in regressing transplantable line-10 tumors in strain-2 guinea pigs. Each of these naturally occurring mono- and diesters contains mixtures of several different mycolic acids. To help determine the structural requirements for tumor regression, 6-monoesters and 6,6-diesters of ,-D-trehalose were prepared synthetically and tested. Esters formed with single types of mycolic acids isolated from Mycobacterium tuberculosis strain Brevannes, when combined with endotoxin and oil droplets, had tumor regressive potency equal to that of the more complex natural products. The synthetic 6,6 trehalose diester of 2-eicosyl-3-hydroxy-tetracosanoic (behenylbehenic) acid, whose structure resembles that of mycolic acid but is of lower molecular weight, provided a cure rate of 60%. However, a similar ester prepared with straight chain docosanoic (behenic) acid was essentially inactive.     

Synthesis and studies of 3'-C-trifluoromethyl-beta-D-ribonucleosides bearing the five naturally occurring nucleic acid bases

3'-C-Trifloromethyl-beta-D-ribonucleoside derivatives bearing the five naturally occurring nucleic acid bases have been synthesized. All these derivatives were prepared by glycosylation reactions of purine and pyrimidine bases with a suitable peracylated 3-C-trifluoromethyl ribofuranose precursor. After deprotection, the resulting title nucleoside analogues were tested for their inhibitory properties against the replication of HIV, HBV and several RNA viruses. However, none of these compounds showed significant antiviral activity.     

Dog models of naturally occurring cancer

Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics.?Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here, we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer.     

Effects of a naturally occurring polyamine on acid secretion by isolated gastric mucosa

Determination of the effects of spermine on acid secretion by isolated rabbit gastric mucosa shows paradoxical responses at neutral luminal pH. Initial inhibition of acid secretion was followed by a return to near basal rates. However, measurement of mucosal and serosal rates of CO2 release indicated that spermine causes prolonged inhibition of acid secretion. Similar prolonged inhibition is seen with mucosa exposed to an acidic luminal pH. The inhibitory effect of spermine is reversed by the addition of K+ to the mucosal side, suggesting spermine interferes with a K+ site at the secretory membrane. Serosal addition of spermine is without effect. The apparent acid secretory rebound phenomenon observed after the addition of spermine is most likely related to formation of H+ in the luminal bathing solution rather than proton secretion by the mucosa.     

The naturally occurring C-17 fatty acid esters of estradiol are long-acting estrogens

C-17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol. A representative component of this family of esters, estradiol-17-stearate, was studied in order to determine the estrogenic properties of these unusual hydrophobic steroids. Following the classical estrogen bioassay, a solution of this ester in oil was injected subcutaneously into immature rats once a day for 3 days. There was little effect on the uterus on the first day after the third injection. However, on subsequent days a large stimulation of uterine growth occurred. The course of this estrogenic effect was exactly opposite to that obtained with estradiol. In order to eliminate the possibility that this effect on the time course of estrogenic stimulation was caused by increased solubility of the hydrophobic esters in the carrier oil, the steroids were administered to adult ovariectomized animals in aqueous medium via a single intravenous injection. The uterotrophic response to estradiol was maximal at 12 h and was completely dissipated in 48-60 h. Estradiol-17-stearate produced a uterotrophic effect of twice the duration of estradiol. In the immature rat, aqueous intravenous injections of estradiol-17-stearate produced a greater uterotrophic effect than estradiol and this effect was still maximal 96 h later. In addition, this single injection of estradiol-17-stearate advanced the time of vaginal opening, a marker for puberty in the female rat. The mechanism of the prolonged estrogenic stimulation was investigated by studying the steroidal content of the uterus after injecting [3H]estradiol and [3H]estradiol-17 -stearate i.v. into immature rats. At 1 and 4 h there was significantly more radioactivity in the uteri of the [3H]estradiol treated animals. At later times (8 h and onwards) the total radioactivity in the uterus did not differ appreciably between the two groups. However at these later times, the amount of [3H]estradiol was far greater in the uteri of animals receiving [3H]estradiol-17-stearate. Consequently, the prolonged estrogenic effects of the endogenous C-17 fatty acid esters of estradiol are caused by the increased duration of the estrogenic signal. It is hypothesized that one of the roles of the fatty acid is to protect the steroid nucleus from metabolism and thereby prolong the life of the parent C18 steroid. Thus, the results of these experiments are consistent with the family of endogenous alkyl esters of estradiol having a physiological role as long-acting estrogens.