Wl. Jin et Z. Lu, Synthesis of a stable form of tertiapin: A high-affinity inhibitor for inward-rectifier K+ channels, BIOCHEM, 38(43), 1999, pp. 14286-14293
Tertiapin (TPN): a small protein derived from honey bee venom, inhibits the
GIRK1/4 and ROMK1 channels with nanomolar affinities. Methionine residue 1
3 in TPN interacts with residue F148 in the channel, located just outside o
f the narrow region of the ROMK1 pore. The methionine residue in TPN can be
oxidized by air, which significantly hinders TPN binding to the channels.
To overcome the reduction in TPN affinity due to oxidation of M13, we repla
ced M13 in TPN with fourteen different residues. Out of the fourteen deriva
tives, only the one in which M13 was replaced by glutamine, TPNQ, binds to
the channel with a K-i value very similar to that of native TPN, Since TPNQ
is stable and functionally resembles native TPN, it will be a very useful
molecular probe for studying the inward-rectifier K+ channels.