The selective S-alkylation of a methionine residue in an elapid venom cardiotoxin.
1. The reaction of cardiotoxin with iodoacetamide or iodomethane at pH 3.0 afforded the corresponding methionine sulphonium derivatives. The major products were S-alkylated at Met-26 whilst the minor products were S-alkylated at both Met-24 and -26. 2. Reaction with iodoacetamide under denaturing conditions led to a reversal of the relative abundances of the two derivatives in the respective reaction mixtures. 3. The derivative S-methylated at Met-26 was about 5-fold less toxic than the parent cardiotoxin. That derivatised at both Met-24 and -26 was non-toxic, indicating the importance of Met-24. 4. The results are discussed in the light of a structural model, previous chemical modifications and 1H-NMR data. It appeared that Met-24 is important for the integrity of an important structural feature of cardiotoxin.
Carlsson
F H
FH
Molecular Biochemistry Division, Council for Scientific and Industrial Research, Pretoria, Republic of South Africa.
D000478:Alkylation; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004546:Elapid Venoms / Q000032:analysis* / Q000633:toxicity; D007460:Iodoacetamide; D007928:Lethal Dose 50; D008715:Methionine / Q000032:analysis*; D008745:Methylation; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D004546:Elapid Venoms; D008715:Methionine; D007460:Iodoacetamide