- Email: [email protected]
Aspects of the pharmacology of Latrodectus mactans venom
REW~WS p ~ , w ~ , M. F. (University of London, Queen Elizabeth College, Department of Physiology, Campden Hill Road, London, WS, England). Aspects of the pharmacology of Latrodectus mactans venom. Gen. Pharmoc. 6, 325-331, 1975. TH~ ^CTION of Latrodectus venom on the neuromuscular junction is entirely pre-synaptic. The end-plate may he protected in acetylcholine synthesis or by reduction in calcium concentration. The action of the venom may be a disruption of the normal carrier mechanisms in the pre-synaptic terminal. S.B.
VINCENt, J.-P., SCHwerrz, H. and LAZDUNSXI,M. (University of Nice, Ctr. for Biochim., UER, SoL Exactes & Nat., Nice, France). Structure-function relationships and site of action of apamin, a neurotoxic polypeptide of bee venom with an action on the central nervous system. Biochemistry 14, 2521-2525, 1975. Ttte FIRSTpart of the paper a'ies to establish correlations between structure and activity of apamin by performing specific modifications. Lys~ was transformed into homuarginine, the two amino groups at position 1 and position 4 (~) were blocked with acetic anhydride or fiuorescamine, the 7-carboxyl group of giutamic acid (7) was reacted with giycine ethyl ester, and hisxa was modified with dicthyl pyrocarbonate. Whereas the derivatives still displayed 40--60~ of the original toxicity, reduction and alkylation of the disulfide bridges, or removal of argl, from acetylated apamin, or oyclohexanidine treatment of argls d- ar&, abolished toxicity. x*C-diacetyl apamin was injected into one mouse, and by far the maximal activity was found in the thoracal and lumbar spinal cord, and hardly any radioactivity was found in the kidney which is well known to concentrate peptides of the size and charge of apamin. The pharrnacokinetics of apamin clearly need closer investigation. E.H. WUNDm~ER, G., MACHLEIDT,W. and W^CHTER, E. (Institut ffir Klinische Chemic and Klinisehe Biochemie, and Iustitut filr Physiologische Chemie und Physikalische Biochemie, University of Munich, Germany). Toxin II from Anemonia sulcata---the first sequence of a coelenterate toxin. Hoppe-Seylers Z. physiol. Chem. 357, 238-240, 1976. THISshort publication is part of an investigation of the tentacle toxins of the sea anemone Anemonia sulcata. Three polypeptides with neuro- and cardio-toxic activities (Toxin I-liD have been isolated (see 13, 359, 1975). Toxin II is made up of 47 amino acid regidues. The sequence from the N-terminal giyoine to the asparagine residue in position 33 was elucidated by automated Edman degradation. Tryptic peptides were separated by ion exchange chromatography and sequenced again by the Edman method. As in some Naja neurotoxins, there is a tryptophane residue near the centre of the peptide chain. On the other hand, no homologies could be detected to the sequences of snake, scorpion or bee venoms. H.M. FRYKLUND, L. and EArd~R, D. (Institute of Biochemistry, University of Uppsala, Uppsala, Sweden). The complete amino acid sequence of a cardiotoxin from the venom of Naja naja (Cambodian cobra). Biochemistry 14, 2860-2864, 1975. The complete covalent structure of a ¢ardiotoxin from the venom of Naja nigrlcoilis (African black-necked spitting cobra). Biochemistry 14, 2865-2871, 1975. THe COMPLETEamino acid sequences of two small, basic proteins with oardiotoxic activity are described. The proteins consist of 60 amino acids in a single pcptide chain cross-linked by four disulfide bridges. Both cardiotoxins have the same pharmacological properties. The LUxoodose for 20-g mice is 15 ~tgfor i.v. injection and 40-50 I~g for i.p. administration. Death is caused by ventricular fibrillation of the heart and usually occurs within 10 min after administration of an LDxoodose. The oardiotoxins were isolated by gel filtration of the crude venom on Sephadcx G-75 followed by gradient ion exchange chromatography on BiD-Rex 70. The sequences were determined using chymotryptic and tryptic peptides from the performic acid oxidized or reduced and S-¢arboxymethylated proteins. The two cardiotoxius arc shown to be homologous to other cardiotoxins and lyric factors from snake venoms and to the functionally distinct curarimimetiz neurotoxins. The disulfide pairing in the N. nigricollis cardiotoxin was established by cleaving the native protein with thermolysin. Even at this structural level there is homology between the cardiotoxius, lyric factors, and neurotoxins, suggesting that the folding of the peptide chains is grossly similar despite differences in pharmacological activity and amino acid sequence. A partial reduction experiment in the absence of denaturing
VINCENt, J.-P., SCHwerrz, H. and LAZDUNSXI,M. (University of Nice, Ctr. for Biochim., UER, SoL Exactes & Nat., Nice, France). Structure-function relationships and site of action of apamin, a neurotoxic polypeptide of bee venom with an action on the central nervous system. Biochemistry 14, 2521-2525, 1975. Ttte FIRSTpart of the paper a'ies to establish correlations between structure and activity of apamin by performing specific modifications. Lys~ was transformed into homuarginine, the two amino groups at position 1 and position 4 (~) were blocked with acetic anhydride or fiuorescamine, the 7-carboxyl group of giutamic acid (7) was reacted with giycine ethyl ester, and hisxa was modified with dicthyl pyrocarbonate. Whereas the derivatives still displayed 40--60~ of the original toxicity, reduction and alkylation of the disulfide bridges, or removal of argl, from acetylated apamin, or oyclohexanidine treatment of argls d- ar&, abolished toxicity. x*C-diacetyl apamin was injected into one mouse, and by far the maximal activity was found in the thoracal and lumbar spinal cord, and hardly any radioactivity was found in the kidney which is well known to concentrate peptides of the size and charge of apamin. The pharrnacokinetics of apamin clearly need closer investigation. E.H. WUNDm~ER, G., MACHLEIDT,W. and W^CHTER, E. (Institut ffir Klinische Chemic and Klinisehe Biochemie, and Iustitut filr Physiologische Chemie und Physikalische Biochemie, University of Munich, Germany). Toxin II from Anemonia sulcata---the first sequence of a coelenterate toxin. Hoppe-Seylers Z. physiol. Chem. 357, 238-240, 1976. THISshort publication is part of an investigation of the tentacle toxins of the sea anemone Anemonia sulcata. Three polypeptides with neuro- and cardio-toxic activities (Toxin I-liD have been isolated (see 13, 359, 1975). Toxin II is made up of 47 amino acid regidues. The sequence from the N-terminal giyoine to the asparagine residue in position 33 was elucidated by automated Edman degradation. Tryptic peptides were separated by ion exchange chromatography and sequenced again by the Edman method. As in some Naja neurotoxins, there is a tryptophane residue near the centre of the peptide chain. On the other hand, no homologies could be detected to the sequences of snake, scorpion or bee venoms. H.M. FRYKLUND, L. and EArd~R, D. (Institute of Biochemistry, University of Uppsala, Uppsala, Sweden). The complete amino acid sequence of a cardiotoxin from the venom of Naja naja (Cambodian cobra). Biochemistry 14, 2860-2864, 1975. The complete covalent structure of a ¢ardiotoxin from the venom of Naja nigrlcoilis (African black-necked spitting cobra). Biochemistry 14, 2865-2871, 1975. THe COMPLETEamino acid sequences of two small, basic proteins with oardiotoxic activity are described. The proteins consist of 60 amino acids in a single pcptide chain cross-linked by four disulfide bridges. Both cardiotoxins have the same pharmacological properties. The LUxoodose for 20-g mice is 15 ~tgfor i.v. injection and 40-50 I~g for i.p. administration. Death is caused by ventricular fibrillation of the heart and usually occurs within 10 min after administration of an LDxoodose. The oardiotoxins were isolated by gel filtration of the crude venom on Sephadcx G-75 followed by gradient ion exchange chromatography on BiD-Rex 70. The sequences were determined using chymotryptic and tryptic peptides from the performic acid oxidized or reduced and S-¢arboxymethylated proteins. The two cardiotoxius arc shown to be homologous to other cardiotoxins and lyric factors from snake venoms and to the functionally distinct curarimimetiz neurotoxins. The disulfide pairing in the N. nigricollis cardiotoxin was established by cleaving the native protein with thermolysin. Even at this structural level there is homology between the cardiotoxius, lyric factors, and neurotoxins, suggesting that the folding of the peptide chains is grossly similar despite differences in pharmacological activity and amino acid sequence. A partial reduction experiment in the absence of denaturing