AG 489

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
CAS Number	128549-96-2 ;
3D model (JSmol)	Interactive image;
ChemSpider	115840 ;
IUPHAR/BPS	2484;
PubChem CID	131007;
UNII	4Q64GNZ7KX ;
CompTox Dashboard (EPA)	DTXSID40155922 ;
	InChI 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) Key: LIURIBSBVUMOJS-UHFFFAOYSA-N ; 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;
	SMILES O=C(NCCCN(O)CCCNCCCNCCCCNCCCN)Cc2c1ccccc1[nH]c2;
Properties
Chemical formula	C26H47N7O2
Molar mass	489.709 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) 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]

Discovery

To identify new inhibitors, capsaicin receptor channels (TRPV₁) were screened with a venom library for activity against these channels. In result, the robust inhibitory activity was found in the venom. Venom fractionation using reversed phase HPLC allowed the purification of two acylpolyamine toxins, AG489 and AG505.^[2]

Chemical structure of agatoxin 505

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.

References

^ 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.
^ ^a ^b 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.
^ 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.
^ 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.

External links

AG+489 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[pmid1519789-1] 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.

[pmid16300403-2] 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.

[1]

[2]

[3]

[4]

Discovery

See also

References

External links