Mutational analysis of the analgesic peptide DrTx(1-42) revealing a functional role of the amino-terminal turn.

PloS One
Ping Li, Shunyi Zhu

Abstract

DrTx(1-42) (a carboxyl-terminally truncated version of drosotoxin) is a potent and selective blocker of tetrodotoxin-resistant (TTX-R) Na(+) channels in rat dorsal root ganglion neurons with analgesic activity. This purpose is to identify key amino acids which are responsible for both blocking and analgesic effects of DrTx(1-42). On the basis of previous study, we designed five mutants of DrTx(1-42) (delN, D8A, D8K, G9A, and G9R) in the amino-terminal turn (N-turn) region, a proposed functional region located in the amino-terminus of the molecule. All these mutants were expressed in E.coli and purified by RP-HPLC. Electrophysiological properties of these analogues were examined by whole-cell patch-clamp recordings and their antinociceptive effects were investigated by the formalin test and acetic acid induced writhing test. All the mutants except for G9A possess a similar secondary structure to that of DrTx(1-42), as identified by circular dichroism analysis. Three mutants (delN, D8A and G9A) were found almost inactive to TTX-R Na(+) channels, whereas D8K retains similar activity and G9R showed decreased potency when compared with the wild-type molecule. Consistent with the electrophysiological observations, D8K and G9R exhibit...Continue Reading

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Citations

Jun 8, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·A C C FreitasM T S Correia

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Datasets Mentioned

BETA
GQ422754

Methods Mentioned

BETA
PCR
circular dichroism

Software Mentioned

Clampex

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