Citation

Elloumi N, Moreau B, Aguiar L, Jaziri N, Sauvage M, Hulen C, Capmau M. Eur. J. Med. Chem. 1992; 27(2): 149-154.

Copyright

(Copyright © 1992, Elsevier Publishing)

DOI

10.1016/0223-5234(92)90103-8

PMID

unavailable

Abstract

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. © 1992.

Language: en

Keywords

article; priority journal; enzyme inhibition; enzyme inhibitor; drug synthesis; structure activity relation; alginates; alginic acid; GDP-mannose dehydrogenase; guanosine; guanosine derivative; oxidoreductase; pseudomonas aeruginosa