Structure-Activity Relationships and Immunochemical Studies on Cobrotoxin
Annual rept. no. 6, 1 Dec 1971-30 Nov 1972
KAOHSIUNG MEDICAL COLL (TAIWAN) DEPT OF BIOCHEMISTRY
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The two-dimensional structure of cobrotoxin has recently been established and permits a study of structure-activity relationships. Preceding studies on the chemical modification of cobrotoxin suggested that either the intact Tyr-25, Lys-47, or Glu-21 is essential for full activity of the toxin. The importance of the single Trp-residue at position 29 for the lethality of cobrotoxin as well as several neurotoxins isolated from the venoms of sea snakes have been reported. The immunodiffusion of these Trp-modified toxins showed similar precipitin lines to those of native toxins. However, as for inducing the production of antibodies in animals by immunization with these modified derivatives and the detail immunochemical studies on these products have not yet been undertaken. In this study, the single Trp-residue in cobrotoxin has been converted into N-formylkynurenine by ozonization, oxidized to oxindole derivative with N-bromosuccinimide, and also modified by reactions with 2- hydroxy-5-nitrobenzyl HNB bromide and 2-nitrophenylsulfenyl chloride. An important feature of the investigation is to determine whether the chemical modification would affect on the antigenic specificity of the toxin.