Rapid practical syntheses of the arginyl polyamine sFTX-3.3: a blocker of voltage-sensitive calcium channels

✍ Scribed by Eduardo Moya; Ian S. Blagbrough

• Publisher: Elsevier Science
• Year: 1994
• Tongue: French
• Weight: 156 KB
• Volume: 35
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)73049-8

✦ Synopsis

Anhropodpolyamine~xinsandthtirsyntheticanalogues~ustfulpharmacological~fa~ idendfication of diffemt types of voltage-sensitive calcium channels [ 1.21. These toxins display a variety of effects~diffaatsubclasgegofcalciumc~~andselectivechannelbbckers~~~inopdnto delineate the physiological functions of these ion channels. Recently, a synthttic polyamine amide .sFIX-3.3 (also called sFTX, arginine polyamiae) (1) and a putative polyamine fium Am&can funnel-web Agclcnopsis upem venom m-3.3 (FlX) (2) have been &own to inhibit voltage-mivated calcium channels. The sekctivityoftbe~polyamineamides remains ill question. Although (2) inhibits P-type calcium CllanlAs [3, 4,5.6]. (1) reversibly inhibits low voltag~~~&ated T-type calcium currents in cultured neumnes at1onM p, 81. Quantities of these spider toxins and synthetic polyamine amides [9] axe required for biological as~ssment and theaefare we have completed the synthesis of (2) [ 101 as well as seeking a facile mute to (1). InthisLe#ar,wtrcpatrapid,~ti~proocdrpesfffthesynthesisof(1).

TbeaminoacidnsidueLargininecontaihstheguanidineof(l)andthereforeanypracticalsynthesiswiunquirethcadditionda (suitablyprotected)~toanactivatcdand~argininegenaatinganewamidebond.