Purotoxin-1 

Selective inhibitor of P2X3 receptors

ATP離子通道P2X3受體選擇性抑制劑

Therapeutic interest : painPurotoxin-1 (PT-1) is a peptide originally isolated from the Central Asian spider Geolycosa sp.  was shown to inhibit selectively P2X3 receptor channels at a 100 nM concentration. Studies were carried-out on cultured rat DRG neurons. Patch-clamp experiments did not show any inhibitory effect of PT-1 on voltage-gated channels (potentials range tested from -100 to 20 mV), neither on TRPV1 (after activation with 500 nM capsaicin). The selectivity of  for P2X3 was highlighted by activating this receptor with 10 µM ATP and 100 µM α, β Methylene-ATP. Indeed, unlike P2X3, P2X2 and heterodimer P2X2/3 are known to be not sensitive to such concentrations. Moreover, P2X3, P2X2, and P2X2/3 are the only known ATP-sensitive receptors expressed in plasma membranes of DRG neurons. So, the observed effect seems to be well related to a selective inhibition of P2X3. P2X3-mediated current was fully inhibited with 100 nM, making it the most potent and selective ligand for P2X3.

P2X3 receptors are known to be implicated in pain mechanisms. Behavioral experimentations carried-out on rat pain models using 0.5 nmol PT-1 injected intraplantar showed to reduce nociception. This anti-nociceptive effect is comparable to A-317491 compound (Abbott's drug) with an amount of almost 3 orders of magnitude lower.

技術(shù)資料

氨基酸序列：

Gly-Tyr-Cys³-Ala-Glu-Lys-Gly-Ile-Arg-Cys¹⁰-Asp-Asp-Ile-His-Cys¹⁵-Cys¹⁶-Thr-Gly-Leu-Lys-Cys²¹-Lys-Cys²³-Asn-Ala-Ser-Gly-Tyr-Asn-Cys³⁰-Val-Cys³²-Arg-Lys-Lys-NH₂ 

二硫鍵：Cys³-Cys¹⁶; Cys¹⁰-Cys²¹; Cys¹⁵-Cys³²; Cys²³-Cys³⁰  

長度 (aa)： 35 

分子式：C₁₅₅H₂₄₈N₅₀O₄₈S₈ 

分子量： 3834.59 Da 

外觀：White lyophilized solid 

可溶性： water and saline buffer 

CAS 號：not available 

來源： Synthetic  

純度： > 97 %

產(chǎn)品信息