The structure of chiriquitoxin from the costa rican frog

Differential binding of tetrodotoxin and its derivatives to voltage‐sensitive sodium channel subtypes (Nav1.1 to Nav1.7)

“…CHTX (2) is a TTX analogue with a glycine functionality connected to C11 (Kao et al, 1981;Yotsu et al, 1990) that is known to inhibit both voltage-sensitive potassium channels and sodium channels (Kao et al, 1981;Yang and Kao, 1992). Our study presents the first investigation of CHTX (2) subtype selectivity.…”

“…The small dihedral angle of HOÀC6ÀC11ÀOH in TTX (1) explains the interaction between these two hydroxyl functionalities and Asp 1717 in domain IV of the VSSC (Lipkind and Fozzard, 1994;Tikhonov and Zhorov, 2005). In contrast, an intramolecular hydrogen bond between C6ÀOH and the carboxyl functionality in CHTX (2), as addressed by Yotsu et al (1990) (Supporting Information Figure S9), indicates a loss of the hydrogen bond between C11ÀOH and Asp 1717 (Choudhary et al, 2003), which explains the finding that CHTX (2) binding affinities for each TTX-sensitive VSSC subtype were one order of magnitude weaker than those of TTX (1) These two consecutive amino acid residues are the key amino acid residues for STX (Walker et al, 2012). The rodent Na v 1.4 has Met 1425 and Asp 1426 at these positions and shows a high affinity for STX, with an IC 50 value of 2.8 ± 0.1 nM, whereas mammalian Na v 1.7 has Thr 1425 and Ile 1426 at those positions and has a low affinity for STX (IC 50 = 702 ± 53 nM).…”

Isolation and Structural Assignment of 11-Nortetrodotoxin-6(S)-ol from the Puffer Arothron nigropunctatus

“…4 ) These analogs modified at C-6 or C-11 still retained significant potency to block sodium channels, and thus were useful to probe the sodium channel molecule. 5 -7) We now report the isolation and structural assignment of 11-norTTX-6(S)-01 (6) from the southern puffer, and the preparation of 6 from 1.…”

The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki : A potent sodium-channel blocker

“…Later in 1975, they identified another guanidinium toxin, tetrodotoxin, as the major alkaloid in aqueous skin extracts of Costa Rican Atelopus varius, whereas a similar guanidinium toxin, chiriquitoxin, was found as the major alkaloid in Costa Rican Atelopus chiriquiensis (3). The structure of chiriquitoxin finally was determined in 1990 (4). The third guanidinium toxin, atelopidtoxin, was the major alkaloid in the Panamanian golden frog A. zeteki (3).…”