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

S J Hodges, A S Agbaji, A L Harvey, R C Hider

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57 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)373-383
Number of pages11
JournalEuropean Journal of Biochemistry
Volume165
Issue number2
Publication statusPublished - 1 Jun 1987

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

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