SELECTIVE DISULFIDE FORMATION IN TRUNCATED APAMIN AND SARAFOTOXIN

Apamin and sarafotoxin are small peptide toxins which are 18 and 21 re sidues long, respectively. They both have cysteines at positions 1, 3, 11, and 15. However, the non-cysteine portions of their sequences and the positions of their disulfides are different. In native apamin, th e cysteines form disulfides 1-11 and 3-15, whereas in sarafotoxin they form the 1-15 and 3-11 pairs. Truncated analogs have been synthesized which lack the carboxyl-terminal tails following cysteine-15. When ox idized by glutathione, both truncated sequences retain the ability to selectively populate the disulfide combination observed in the respect ive full-length parent. This ability is retained in the presence of th e denaturing agent 5 M guanidinium chloride. Circular dichroism spectr a of the nativelike isomers are nearly identical to those of the paren t sequence, and are not affected by heating to 75-degrees-C or exposur e to 5 M guanidinium chloride. The alpha helix observed in apamin is a consequence of both the disulfide topology and the non-cysteine porti ons of the sequence. There is not much a helix when apamin is forced t o adopt the disulfides found in native sarafotoxin or when sarafotoxin is forced to adopt the disulfides found in native apamin.