Repozytorium publikacji - Politechnika Gdańska

In search for new effective we antyfungals we focus on two enzymes involved in biosynthesis of the fungal cell wall. The first enzyme is glucosamine-6-phosphate (GlmS), which catalyzes transformation of D-fructose-6-phosphate (Fru-6P) to D-glucosamine-6-phodphate (GlcN-6P) in the chitin biosynthesis pathway. The second enzyme is phosphomannose isomerase (PMI) repored to play a crucial role in biosynthesis of many mannosylated structures, including cell wall components of fungi. PMI is aldose-ketose isomerase and catalyzes reversible isomeration of D-manno-6-phosphate (Man-6P) to D-fructose-6-phosphate (Fru-6P). Both enzymes are proposed as the targetes for antifungal chemotherapy and a search fpr their selective inhibitors is continued. Mechanisms of the reactions catalyzed by both enzymes are known and similar. The reaction performed by GlmS is believed to proceed through the formation of an imine intermediate (1), whereas the reaction catalyzed by PMI proceeds via a cis-endiol intermediate (2). In search of mimetics of intermediates 1 and 2 we synthesize phosphono and phosphate derivatives of the hydroxyiminoo-D-glucitols. Similary in the structure of the planed compounds to intermediates 1 and 2 allow us to assume that they can be the potential inhibbitors of the both enzyme. Dimethyl and diethyl ester analogs will have more lipophilic character, which make them easier to penetrate through the cytoplasmic call membrane. It was proved that similar esters are hydrolyzed inside a cell. Here, the completed stages of our synthases are presented.

Autorzy

• Magdalena Cyman,
• Henryk Myszka,
• mgr inż. Karolina Kwiatkowska-Semrau link otwiera się w nowej karcie ,
• prof. dr hab. inż. Sławomir Milewski link otwiera się w nowej karcie ,
• Beata Liberek