Cardiotoxin VI4 from Naja mossambica mossambica crystallizes in space group P61 (a b = 73.9 A; c = 59.0 A) with two molecules of toxin (molecular mass = 6715 Da) in the asymmetric unit. The structure was solved by using a combination of multiple isomorphous replacement and density modification methods. Model building and least-squares refinement led to an agreement factor of 27% for a data set to 3-A resolution prior to any inclusion of solvent molecules. The topology of the molecule is similar to that found in short and long snake neurotoxins, which block the nicotinic acetylcholine receptor. Major differences occur in the conformation of the central loop, resulting in a change in the concavity of the moleculq. Hydrophobic residues are clustered in two distinct areas. The existence of stable dimeric entities in the crystalline state, with the formation of a six-stranded antiparallel (3 sheet, may be functionally relevant.Snake venom toxins form a large group of homologous proteins that can be subdivided into three main classes: long neurotoxins (71-74 amino acid residues, five disulfide bridges); short neurotoxins and cardiotoxins (60)(61)(62) residues, four disulfides). Cardiotoxins from Elapidae venoms are basic proteins and are relatively less toxic than the related neurotoxins. They represent >50% of the whole venom of Naja mossambica mossambica. Cardiotoxin V"14 is isolated from Naja m. mossambica (1). It is a minor component and is characterized by the absence of tryptophan and phenylalanine residues.Although they are similar in peptide chain length and sequence, short neurotoxins and cardiotoxins have pharmacologically distinct effects. Neurotoxins block nicotinic acetylcholine receptors (2); cardiotoxins owe their name to their toxic effect on the heart (3). However, they are really cytotoxins since they perturb the membrane structure of all types of excitable and nonexcitable cells (for a review, see ref. 4). Interactions with membrane lipids are certainly of crucial importance in their mode of action (5-8). This interaction with membrane lipids is followed by an indirect inhibition of the Na',K+-ATPase, which probably plays a central role in the cytotoxicity of this peptide family.Primary sequence analyses have shown a high degree of homology within each of the three classes of snake toxins (9) and also between these classes. The homology between neurotoxins and cardiotoxins is essentially due to the similar location of the four disulfide bridges. This sequence homology contrasts with the completely different modes of action of the two types of toxins. Cardiotoxins do not prevent association of neurotoxins with the nicotinic acetylcholine receptor, and neurotoxins are not cytotoxic.The three-dimensional (3D) structures of two snake neurotoxins are known from x-ray crystallographic studies: erabutoxin from Laticauda semifasciata venom (10, 11) and a-cobratoxin from Naja naja siamensis (12 Crystallization and Structure DeterminationCardiotoxin was purified from Naja m. mossambica venom acc...

No abstract

The effect of tBuP4, a strong and cation-free base, on the yield and diastereoselectivity of additions of thus formed "naked" alpha-sulfonyl carbanions to achiral butyraldehyde and chiral isopropylideneglyceraldehyde was studied. It has been found that with tBuP4 a reasonable yield ( approximately 55%) and a slightly better diastereoselectivity (72% of the anti diastreomer) are obtained with achiral and nonfunctionalized butyraldehyde while with isopropylideneglyceraldehyde the use of tBuP4 allowed us to greatly increase the yields (up to 95-100%) and the diastereoselectivities (83-89% of a single diastereomer over the four possible diastereomers). It was also shown that the extra oxygen atom in the alpha-position plays a determinant role in this effect.

Addition of halogens and pseudohalogens across one -bond of l,4-dichlorobut-2-yne, followed by a 1,4elimination, is an efficient synthesis of several new polysubstituted butadienes. If the product dienes have a sulfur or selenium substitutent they are quite reactive, undergoing cycloaddition with the moderately reactive dienophile methyl vinyl ketone at 20 °C in the presence of boron trifluoride etherate. The regiochemistry of the cycloadditions was elucidated, and the limitations of the methodology are discussed.

The thermolytic decomposition of citric acid in the presence of tin/lead solder has been investigated. The solid reaction products were first examined by solid-state 13C NMR. The samples were then dissolved in D2O, and 1H and 13C 1D and 2D (HMQC, TOCSY) spectra were obtained. Results indicate the presence of a series of compounds including 3-hydroxyglutaric, citraconic, itaconic and aconitic acids, and anhydrides. Solution- and solid-state NMR data are provided for citric acid and a number of metal and alkali metal citrate salts. Results of this work are related to the use of citric acid as a solder flux and to the elimination of chlorofluorocarbon cleaning processes in the electronics industry.