Actin-targeting natural products: structures, properties and mechanisms of action

Natural small-molecule inhibitors of actin cytoskeleton dynamics have long been recognized as valuable molecular probes for dissecting complex mechanisms of cellular function. More recently, their potential use as chemotherapeutic drugs has become a focus of scientific investigation. The primary focus of this review is the molecular mechanism by which different actin-targeting natural products function, with an emphasis on structural considerations of toxins for which high-resolution structural information of their interaction with actin is available. By comparing the molecular interactions made by different toxin families with actin, the structural themes of those that alter filament dynamics in similar ways can be understood. This provides a framework for novel synthetic-compound designs with tailored functional properties that could be applied in both research and clinical settings. Received 6 April 2006; received after revision 31 May 2006; accepted 19 June 2006     

Immunological properties of oxygen-transport proteins: hemoglobin,hemocyanin and hemerythrin

It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.     

Comparison of dihydrodiazepam enantiomers: Metabolism,serum binding and brain receptor binding

Summary Dihydrodiazepam is a diazepam prodrug, as shown by its in vitro metabolism by rat and mouse liver and brain microsomal fractions, and its displacing activity on brain diazepam binding. The mechanism of bioactivation is discussed. Stereoselectivity of metabolism and of binding to specific benzodiazepine binding sites in brain synpatosomes and serum albumin were studied.Acknowledgment. The authors are grateful to Dr. J. Wolford for the synthesis of³H-diazepam.     

Chromatographic purification,crystallization and study of vegetablel-alanine: 2-oxoglutarate-aminotransferase properties

Zusammenfassung l-Alanin-2 Oxoglutarataminotransferase aus Soya,Glycine hispida, wurde 230fach gereinigt und kristallisiert sowie einige physikalisch-chemische Eigenschaften (Michaelis Konstante, spezifische Wirkung, pH, Temperatureinfluss, ionale Wirkungen und Metaboliten) wurden studiert.     

Elastase,collagenase and the radial elastic properties of arteries

Summary Studies were performed on 203 pairs of dog carotid arteries subjected to unidirectional radial compression. Treatment with 80 U/ml purified elastase for 90 min decreased radial stress, but treatment with 640 U/ml collagenase for 90 min did not. These data suggest that elastin, but not collagen, contributes to wall resistance to radial compression.     

Elastase, collagenase and the radial elastic properties of arteries

Studies were performed on 203 pairs of dog carotid arteries subjected to unidirectional radial compression. Treatment with 80 U/ml purified elastase for 90 min decreased radial stress, but treatment with 640 U/ml collagenase for 90 min did not. These data suggest that elastin, but not collagen, contributes to wall resistance to radial compression.     

Hydroxyapatite: Preparation and properties

Zusammenfassung Es wurden sowohl ältere als auch neuere Verfahren zur Fällung von Kalziumhydroxyapatit aus wässriger Lösung vergleichend überprüft und die erhaltenen Präparate mittels chemischer und physikalischer Methoden charakterisiert, wobei sich ergab, dass das vom National Bureau of Standards entwickelte Verfahren die am besten definierten Kristalle liefert.

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Acknowledgment. The authors are indebted to the late Dr.R. V. Coates for the X-ray diffraction analyses and to Mr.R. D. Woods, Department of Plant Pathology, Rothamsted Experimental Station for the electron micrographs.     

Purification and some properties of hemagglutinin from the Myxomycete,Physarum polycephalum

A new hemagglutinin was isolated from the plasmodium ofPhysarum polycephalum by salting out with ammonium sulphate followed by chromatography on DE-32, DEAE-Toyopearl and hydroxyapatite. This hemagglutinin, named physarumin, was purified 1000-fold over crude extracts. The molecular weight of physarumin was determined to be 22,000 by size exclusion chromatography on Bio-Gel P-60 and 8,700 by SDS-polyacrylamide gel electrophoresis. Physarumin agglutinated rabbit, guinea pig, horse and human erythrocytes. Physarumin-induced hemagglutination was inhibited by fetuin and ₁ glycoprotein, but not by commercially available mono-and disaccharides. Hemagglutinating activity was blocked by EDTA, and was restored by adding Ca²⁺ but not by Mg²⁺.