ENGINEERING OF CARDIOTOXIN BY CHEMICAL SYNTHESIS .1. RAPID SYNTHESIS OF FULLY ACTIVE CARDIOTOXIN-II AND CARDIOTOXIN-IV OF TAIWAN COBRA VENOM

Two 60-residue snake toxins with four disulfide bridges, cardiotoxin T I and IV, of Taiwan cobra (Naja naja atra) have been rapidly prepared in overall yields of 3.9% (cardiotoxin II) and 3.7% (cardiotoxin IV) w ithin three weeks using the chemical method. Physicochemical character ization of these synthetic cardiotoxins was carried out by amino acid analysis, mass spectroscopy, capillary electrophoresis, peptide mappin g, circular dichroism spectroscopy, and lethal toxicity. As compared w ith natural cardiotoxins, the results indicated that the synthetic car diotoxins possessed the same physicochemical properties as those of na tural ones. Therefore, in addition to preparation of various important toxins with satisfactory quantities for biochemical and pharmacologic al studies within a short time, this rapid method also provides an imp ortant route to obtain many interesting toxins and designed toxin anal ogues for structure/function relationship studies in the near further.