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
References
Sep 1, 1967·British Journal of Anaesthesia·A H Masson
Jan 11, 1980·European Journal of Pharmacology·R DeraedtM Flahaut
Mar 9, 1999·FEBS Letters·A N AkopianJ N Wood
Jun 3, 1999·Pain·V MartínezE A Mayer
Aug 17, 1999·Nature Neuroscience·A N AkopianJ N Wood
Nov 27, 2001·Life Sciences·Y IkedaS Oh-ishi
Jun 25, 2004·Journal of Pharmacological Sciences·Akiko SakaueHideki Ono
Sep 14, 2004·Journal of Neurobiology·John N WoodMark D Baker
Nov 19, 2004·The Journal of Biological Chemistry·Yucheng XiaoSongping Liang
Dec 6, 2005·Toxicon : Official Journal of the International Society on Toxinology·Cheng-Zhong WangCheng-Wu Chi
Dec 31, 2005·Pharmacological Reviews·William A CatterallStephen G Waxman
Aug 22, 2006·The International Journal of Biochemistry & Cell Biology·J Ekberg, D J Adams
Oct 13, 2006·Journal of Ethnopharmacology·Niele Matos GomesPatricia Dias Fernandes
Nov 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·J EkbergR J Lewis
Jan 24, 2007·Toxicon : Official Journal of the International Society on Toxinology·William A CatterallTodd Scheuer
Oct 24, 2007·The International Journal of Biochemistry & Cell Biology·J EkbergD J Adams
Jan 25, 2008·Proteins·Céline LandonFrançoise Vovelle
Feb 19, 2008·Biochimica Et Biophysica Acta·Stefania RomeoLourival D Possani
Feb 22, 2008·Molecular Immunology·Shunyi ZhuRichard L Gallo
Jul 25, 2008·Insect Molecular Biology·B Gao, S-Y Zhu
Sep 11, 2008·Current Pharmaceutical Design·Bert BillenJan Tytgat
Jul 8, 2009·Journal of Ethnopharmacology·Okan ArihanMustafa Ilhan
Apr 28, 2010·Developmental and Comparative Immunology·Zhenting Zhang, Shunyi Zhu
Jul 20, 2010·Biochemical Pharmacology·Shunyi ZhuJan Tytgat
Sep 22, 2010·The International Journal of Biochemistry & Cell Biology·Kristopher SilverJames D Lillich
Nov 3, 2010·Biochemical Pharmacology·Shunyi ZhuYuzhe Yuan
May 17, 2011·PloS One·Yao-Qing YuJun Chen