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Cobra cardiotoxins. Purification, effects on skeletal muscle and structure/activity relationships

Hodges, S J and Agbaji, A S and Harvey, A L and Hider, R C (1987) Cobra cardiotoxins. Purification, effects on skeletal muscle and structure/activity relationships. European Journal of Biochemistry, 165 (2). pp. 373-383. ISSN 0014-2956

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Abstract

A new preparative method for isolating homogeneous cardiotoxins from cobra venoms is described. The technique, based on reverse-phase high-pressure liquid chromatography, was used to isolate eight cardiotoxins of known sequence from four different venoms. In each case the method was found to be particularly efficient at removing trace quantities of contaminating phospholipase. Cardiotoxins isolated in this manner were found to retain their full biological activity. Without exception the purified cardiotoxins lacked powerful haemolytic activity at concentrations up to 0.01 mM (about 100 micrograms ml-1), although some lysis of human erythrocytes was induced at higher concentrations. The cardiotoxins displayed a wide range of depolarizing activity on cultured skeletal muscle, the lowest activity being associated with the highest LD50 value. Correlating variations in amino acid sequence and variations in depolarization potency revealed the importance of residues in the second and third loops, especially lysine-46, serine-48 and lysine-52, together with a number of hydrophobic residues. Further modifications of pharmacological activity were associated with the presence of additional basic residues in the first and second loops and to minor differences in secondary structure.

Item type: Article
ID code: 31691
Keywords: amino acid sequence, amino acids, animals, chick embryo, chromatography, circular dichroism, cobra cardiotoxin proteins, cobra venoms, erythrocytes, humans, hydrolysis, isoelectric focusing, muscles, phospholipases A, structure-activity relationship, Pharmacy and materia medica, Biochemistry
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 13 Jul 2011 09:57
    Last modified: 05 Sep 2014 09:34
    URI: http://strathprints.strath.ac.uk/id/eprint/31691

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