Receptor-based assays.

Receptor-based assays have benefitted from the newest advances in biotechnology and electronics in three main ways: genetically engineered cells expressing single receptor subtypes have been developed for many natural and synthetic ligands; assays have been designed which take advantage of a variety of signals triggered in cells by binding, or inhibition of binding, of ligands to surface-bound receptors; and radiolabelled ligand assays have been considerably improved and simplified by novel electronic devices.     

Alternative sources of biologically active substances

The majority of antibiotics and substances with diverse biological activity used in medicine are produced by actinomycetes, nonfilamentous bacteria and fungi. Other microorganisms, such as myxobacteria, pseudomonads, nocardias, basidiomycetes, marine microorganisms, enterobacteria, halobacteria, hyperthermophiles etc. are investigated for new biologically active metabolites.     

Placenta--a source of biologically active substances

In the review there are some data displaying the scientific and patent literature presenting placenta as a rich source of some biologically active substances (BAS): proteins, lipids, enzymes, glycolipids and glycolipoproteins, hormones. This information is capable to be used while developing the techniques of BAS producing from placenta in order of creating the organospecific complex preparations with medically-preventive properties.     

PASS: prediction of activity spectra for biologically active substances

The concept of the biological activity spectrum was introduced to describe the properties of biologically active substances. The PASS (prediction of activity spectra for substances) software product, which predicts more than 300 pharmacological effects and biochemical mechanisms on the basis of the structural formula of a substance, may be efficiently used to find new targets (mechanisms) for some ligands and, conversely, to reveal new ligands for some biological targets. We have developed a WWW interface for the PASS software. A WWW server for the on-line prediction of the biological activity spectra of substances has been constructed.     

Polyelectrolyte microcapsules as the systems for delivery of biologically active substances

Based on the method of the layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, sodium alginate (Alg) and poly-L-lysine (PLL), novel biodegradable microcapsules have been prepared for delivery of biological active substances (BAS). Porous spherical CaCO₃ microparticles were used as templates. The template cores were coated with several layers of oppositely charged polyelectrolytes forming shell on the core surface. The core-shell microparticles were converted into hollow microcapsules by means of core dissolution with EDTA. Mild conditions for microcapsules preparation allow to perform incorporation of various biomolecules maintaining their bioactivity. Biocompatibility and biodegradability of the polyelectrolytes give a possibility to use the microcapsules as the target delivery systems. Chymotrypsin entrapped into the microcapsules was used as a model enzyme. The immobilized enzyme retained about 86% of the activity compared to a native chymotrypsin. The resultant microcapsules were stable in acidic medium and could be easily decomposed by trypsin treatment in slightly alkaline medium. Chymotrypsin was shown to be active after its release from the microcapsules decomposed by the trypsin treatment. Thus, the microcapsules prepared by the LbL technique can be used for the development of new type of BAS delivery systems in humans and animals.     

Quantitative NMR spectroscopy of biologically active substances and excipients

Biologically active ingredients and excipients are the essentials of a drug formulation, such as a tablet, dragee, solution, etc. Quality control of such substances thus plays a pivotal role in the production process of pharmaceutical drugs. Since these agents often exhibit complex structures, consist of multiple components, or lack of a chromophore, traditional means of characterization are often not feasible. Furthermore, substances of small molecular weight or strong polar character generally exhibit poor chromatographic properties, thus, conventional procedures such as high-performance liquid chromatography are often not applicable. Instead, quantitative nuclear magnetic resonance (qNMR) spectroscopy has emerged as an alternative or orthogonal method in drug analysis. In this review, we elaborate on the application of qNMR to three important classes of biological substances, namely polysaccharides, amino acids, and lipids, and demonstrate the benefits of this modern tool in contrast to traditional techniques.     

Evidence for several types of biologically active substances in north pacific sea anemones

1. Twenty-two sea anemone samples from seven species were collected in Aleutian and Comandorskiye Islands from sub-littoral region (> 50 m depth).2. Water-ethanol extracts of sea anemones were tested using various test-systems after ethanol evaporation.3. All sea anemones extracts inhibited DNA and most of them inhibited RNA synthesis in Ehrlich carcinoma tumor cells.4. Extracts of most sea anemones species showed high hemolytic activity.5. The extracts proved to be nontoxic or display low toxicity being i.p. injected into mice.6. Some extracts precipitated virus of aleutian disease of mink.7. None of the extracts showed activity toward Gram + ve, Gram −ve bacteria or yeast.     

Chemically defined medium for the production of biologically active substances of CHO cells

A recombinant CHO cell line (GT19) secreting a high level of human growth hormone (hGH) was constructed with amplification of the introduced hGH gene. The cells grew well in the alpha MEM medium supplemented with 5% dialyzed fetal calf serum (dFCS), but not with less than 1% dFCS. Therefore we examined various medium components and obtained an improved medium which supported cell growth at low serum concentrations. The production of hGH by the cells was also enhanced in this medium.Abbreviations CHO Chinese hamster ovary - hGH human growth hormone - dFCS dialyzed fetal calf serum - dhfr dihydroforate reductase - MTX methotrexate     

Effect of dilute solutions of biologically active substances on cell membranes

The article presents data on changes in physicochemical properties of different biological membranes (plasmatic, microsomal, synaptosomes) under the action of biologically active substances, which are different in their chemical structure and the mechanism of action (natural and synthetic antioxidants, thyrotropin - releasing hormone, phorbol esters), in the wide range of concentrations (10^?22?10^?3 M). Dose dependences of the effect of biologically active substances on the activity of membrane-bound enzymes, lipid peroxidation, the structural state of the various regions of the lipid bilayer of membranes have been obtained and analyzed in terms of their formal generality of polymodality, number and position of the maxima, a sign change of the effect. An attempt to explain the mechanism of each of the observed peaks in these curves has been made. The maximum in the range of relatively high “physiological” concentrations (10^?3–10^?7 M) is associated with introduction of biologically active substances into biomembranes. In this study maxima in the range of ultra-low doses (10^?11–10^?16 M) and “apparent” concentrations (10^?18 M), where the presence of biologically active substance molecule in a reaction volume is probabilistic in nature, are explained by physicochemical properties of diluted biologically active substances solutions. This conclusion is based on our data on the changes in IR spectra of aqueous solutions of biologically active substances and the results obtained by academician A.I. Konovalov et al. concerning the physicochemical properties of dilute solutions of biologically active substances (conductivity, surface tension, charge), due to the formation of so-called “nanoassociates” from biologically active substance molecule and numerous number of water molecules. The nanoassociates formation and biological effect disappear if the low concentration solutions are kept in a special shielded permalloy container protecting its contents from external electromagnetic field. Thus, nanoassociates are the material carriers of the unique ability of the ultra-low doses of biologically active substances to exhibit biological effects.