Preparation and activity of guanidinated or acetylated erabutoxins

Abstract

Eurabutoxins a, b and c, neurotoxic proteins of a sea snake Laticauda semifasciata, were guanidinated with O-methylisourea. The amino groups of all the lysine residues and those at the N-termini of the toxins were modified. The lethal activity [to mice] of the toxins decreased to 50% (erabutoxins a and b) or 17% (erabutoxin c) of the original value on the modification. The c.d. (circular dichroism) maximum at 227 nm of the modified toxins became lower, whereas the whole profile of the c.d. curve remained unchanged. The amino groups of erabutoxin b were acetylated with acetic anhydride. All 5 monoacetyl derivatives were isolated from the reaction products by CM-cellulose and Bio-Rex 70 column chromatography. [1-N.alpha.-acetylarginine]-, [15-N6-acetyl-lysine]- and [51-N6-acetyl-lysine]-erabutoxin b retained the toxicity of the native toxin, whereas [27-N6-acetyl-lysine]- and [47-N6-acetyl-lysine]-erabutoxin b were 17 and 8% active, respectively. The overall profile of the c.d. spectrum of erabutoxin b remained unchanged on the monoacetylation.