AG 489
Names
Preferred IUPAC name
N-(20-Amino-4-hydroxy-4,8,12,17-tetraazaicosan-1-yl)-2-(9H-purin-3-yl)acetamide
Other names
Agatoxin 489
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C26H47N7O2/c27-11-5-14-28-12-3-4-13-29-15-6-16-30-17-7-19-33(35)20-8-18-31-26(34)21-23-22-32-25-10-2-1-9-24(23)25/h1-2,9-10,22,28-30,32,35H,3-8,11-21,27H2,(H,31,34) checkY
    Key: LIURIBSBVUMOJS-UHFFFAOYSA-N checkY
  • InChI=1/C26H47N7O2/c27-11-5-14-28-12-3-4-13-29-15-6-16-30-17-7-19-33(35)20-8-18-31-26(34)21-23-22-32-25-10-2-1-9-24(23)25/h1-2,9-10,22,28-30,32,35H,3-8,11-21,27H2,(H,31,34)
    Key: LIURIBSBVUMOJS-UHFFFAOYAP
  • O=C(NCCCN(O)CCCNCCCNCCCCNCCCN)Cc2c1ccccc1[nH]c2
Properties
C26H47N7O2
Molar mass 489.69708
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

AG 489 (or agatoxin 489) is a component of the venom produced by Agelenopsis aperta,[1] a North American funnel web spider. It inhibits the ligand gated ion channel TRPV1 through a pore blocking mechanism.[2]

To identify new inhibitors, capsaicin receptor channels (TRPV1) were screened from a venom library for activity against these channels. In result, the robust inhibitory activity was found in the venom. Venom fractionation utilizing a reversed phase HPLC [2] which led to the purification of the two acylpolyamine toxins, AG489 and AG505. Both of these inhibit the TRPV1 channels [3] from the extracellular membrane side. From the pore blocking mechanism, the pore mutations that change toxic affinity were identified. As a result, the four mutants decreased toxic affinity and several mutants increased it. Therefore, this was consistent with the scanned TM5-TM6 linker region [4] being the outer vestibule of the channels and further confirming that AG489 is a pore blocker.

See also

References

  1. ↑ Herold EE, Yaksh TL (September 1992). "Anesthesia and muscle relaxation with intrathecal injections of AR636 and AG489, two acylpolyamine spider toxins, in rat". Anesthesiology. 77 (3): 507–12. doi:10.1097/00000542-199209000-00016. PMID 1519789.
  2. 1 2 Kitaguchi T, Swartz KJ (November 2005). "An inhibitor of TRPV1 channels isolated from funnel Web spider venom". Biochemistry. 44 (47): 15544–9. doi:10.1021/bi051494l. PMID 16300403.
  3. ↑ Kaneko Y, Szallasi A (May 2014). "Transient receptor potential (TRP) channels: a clinical perspective". British Journal of Pharmacology. 171 (10): 2474–507. doi:10.1111/bph.12414. PMC 4008995. PMID 24102319.
  4. ↑ Winter Z, Buhala A, Ötvös F, Jósvay K, Vizler C, Dombi G, et al. (June 2013). "Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel--an overview of the current mutational data". Molecular Pain. 9: 30. doi:10.1186/1744-8069-9-30. PMC 3707783. PMID 23800232.


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