INHIBITORS OF GDP MANNOSE DEHYDROGENASE OF PSEUDOMONAS-AERUGINOSA MUCOID STRAINS

The synthesis of 5'-amino-5'-deoxy guanosine was improved in order to use it for elaboration of liposolubles GDP-mannose analogues. GDP-mannose is the substrate of GDP-mannose dehydrogenase, a key enzyme in the alginates biosynthetic pathway of Pseudomonas aeruginosa mucoid strains. Guanosine, 5'-amino-5'-deoxy-guanosine, 5'-(3-hydroxypropyl)-amino-5'-deoxy-guanosine and 2 GDP mannose analogues were tested on the GDP mannose dehydrogenase activity. The more potent inhibitor was the GDP-mannose analogue where mannose is substituted by a 6-ethynyl derivative, linked to an N2-acetyl-2', 3'-O-isopropylidene guanosine by a sulfonyl amino carbonyl arm. As a hypothesis, this compound could be a suicide or irreversible inhibitor for the enzyme.