Structure-antibiotic activity relationships of brevinin-1 and thanatin containing Rana box = Rana Box를 포함한 Brevinin-1 및 Thanatin의 구조-항생활성 상관관계

Abstract

In order to investigate structure-antibiotic activity relationships of brevinin-1 and thanatin containing Rana box composed of basic loop formed by disulfide bridge in their carboxy terminus, thanatin, brevinin 1 and their analogues (T-B1, T-B2 and B-T) in which their Rana box sequence exchanged was designed and synthesized by the solid phase method using Fmoc-chemistry. The basic sequence of Rana box of thanatin had more significant effect on both antibacterial and antifungal activity than that of brevinin 1. The tail sequence (QRM) of thanatin was found to be important in its antibacterial and antifungal activity. Rana box sequence of brevinin-1 did not have a significant effect on its antitumor and phospholipid vesicle-aggregating activities. Brevinin-1 showed stronger α-helical structure in the membrane- mimicking environment such as SDS micelle than thanatin. A remarkable increase in α-helicity of T-B1 and T-B2 caused a significant reduction on antibacterial and antifungal activities. In contrast, a little decrease in α-helicity of B-T caused 4-fold reduction on antibacterial activity. These results suggested that the α-helicity of brevinin-1 plays more important role in antibiotic activity than that of thanatin. Furthermore, antibacterial activity of thanatin against E. coli resulted from the disruptive effect against the outer cell membrane of E. coli.