Repozytorium publikacji - Politechnika Gdańska

Amphotericin B (AmB) is an effective but very toxic antifungal antibiotic. In our laboratory a series of AmB derivatives of improved selectivity of action was synthesized and tested. To understand molecular basis of this improvement, comparative conformational studies of amphotericin B and its two more selectivederivatives were carried out in an aqueous solution and in a lipid membrane. These molecular simulation studies revealed that within a membrane environment the conformational behavior of the derivatives differs significantly from the one observed for the parent molecule. Possible reasons for such a difference are analyzed. Furthermore, we hypothesize that the observed conformational transition within the polar head of AmB derivatives may lead to destabilization of antibiotic-induced transmembrane channels. Consequently, the selective toxicity of the derivatives should increase as ergosterol-rich liquid-ordered domains are more rigid and conformationally ordered than their cholesterol-containing counterparts, and as such may better support less stable channel structure.

Autorzy

• prof. dr hab. inż. Jacek Czub link otwiera się w nowej karcie ,
• Anna Neumann,
• prof. dr hab. inż. Edward Borowski link otwiera się w nowej karcie ,
• prof. dr hab. inż. Maciej Bagiński link otwiera się w nowej karcie