PON1 enzimi üzerine DT-15-Crown-5 taç eterinin etkisinin araştırılması

Adem Ergün, Baki Çiçek

Öz


İnsan serum paraoksonaz 1 (PON1, EC3.1.8.1) HDL'ye bağlı olan, aktif bölgesinde kalsiyum içeren, organofosfat ajanlarını ve sinir gazlarını hidroliz eden, LDL'nin oksidasyonu ile lipit peroksitlerin oluşumuna ve bakteri endotoksinlerine karşı koruyucu etkisi olan önemli bir karaciğer enzimidir.  Çalışmamızda, PON1 enzimi daha önceden sentezi yapılmış, sepharose-4B-L-tirosin-1-naftilamin jeli kullanılarak hidrofobik etkileşim kromatografisi ile tamamen saflaştırılmıştır.  Enzimin saflık kontrolü de SDS – PAGE ile yapılmıştır. İnhibisyon ajanı olarak kullanılmak üzere 7,13-dithio-1,4,10-trioksasiklopentadekan (DT-15-Crown-5) tiyo taç eteri SN2 mekanizmasına göre halka kapama reaksiyonu sonucunda sentezlendi.  DT-15-Crown-5’in paraoksanaz enzimi üzerinde kuvvetli inhibisyon etkisi gözlendi.  DT-Taçeterin PON1 ile inhibisyon değeri (IC50) 22,62 M olarak tespit edildi.


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