AG 489
{{chembox
| Verifiedfields = changed
| verifiedrevid = 477235479
| ImageFile=Agatoxin 489.svg
| ImageSize=300px
| PIN=N-(20-Amino-4-hydroxy-4,8,12,17-tetraazaicosan-1-yl)-2-(9H-purin-3-yl)acetamide
| OtherNames=Agatoxin 489
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 2484
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 115840
| 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)
| InChIKey = LIURIBSBVUMOJS-UHFFFAOYAP
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LIURIBSBVUMOJS-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|changed|??}}
| CASNo=128549-96-2
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4Q64GNZ7KX
| PubChem=131007
| SMILES = O=C(NCCCN(O)CCCNCCCNCCCCNCCCN)Cc2c1ccccc1[nH]c2
}}
|Section2={{Chembox Properties
| C = 26 | H = 47 | N = 7 | O = 2
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
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|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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AG 489 (or agatoxin 489) is a component of the venom produced by Agelenopsis aperta,{{cite journal | vauthors = Herold EE, Yaksh TL | title = Anesthesia and muscle relaxation with intrathecal injections of AR636 and AG489, two acylpolyamine spider toxins, in rat | journal = Anesthesiology | volume = 77 | issue = 3 | pages = 507–12 | date = September 1992 | pmid = 1519789 | doi = 10.1097/00000542-199209000-00016 }} a North American funnel web spider. It inhibits the ligand gated ion channel TRPV1 through a pore blocking mechanism.{{cite journal | vauthors = Kitaguchi T, Swartz KJ | title = An inhibitor of TRPV1 channels isolated from funnel Web spider venom | journal = Biochemistry | volume = 44 | issue = 47 | pages = 15544–9 | date = November 2005 | pmid = 16300403 | doi = 10.1021/bi051494l }}
Discovery
{{unclear-section|date=July 2024}}
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.
:File:Agatoxin 505.svg{{clear-left}}
Both of these inhibit the TRPV1 channels{{cite journal | vauthors = Kaneko Y, Szallasi A | title = Transient receptor potential (TRP) channels: a clinical perspective | journal = British Journal of Pharmacology | volume = 171 | issue = 10 | pages = 2474–507 | date = May 2014 | pmid = 24102319 | pmc = 4008995 | doi = 10.1111/bph.12414 }} 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{{cite journal | vauthors = Winter Z, Buhala A, Ötvös F, Jósvay K, Vizler C, Dombi G, Szakonyi G, Oláh Z | display-authors = 6 | title = Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel--an overview of the current mutational data | journal = Molecular Pain | volume = 9 | pages = 30 | date = June 2013 | pmid = 23800232 | pmc = 3707783 | doi = 10.1186/1744-8069-9-30 | doi-access = free }} being the outer vestibule of the channels and further confirming that AG489 is a pore blocker.
See also
References
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External links
- {{MeshName|AG+489}}