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.