Pseudomonas aeruginosa is an opportunistic bacterium showing increasing resistance to antibiotics and consequently represents elevated threatening problems in hospital environments, particularly for cystic fibrosis patients. The use of glycomimetics as an anti-adhesive strategy against microorganisms may complement the use of antibiotics. PA-IIL lectin (LecB) from P. aeruginosa constitutes an appealing target for antibacterial agents, as it has been proposed to play a key role in binding to airway epithelia and/or to be involved in biofilm formation. The lectin has an unusually high affinity for L-fucose and related oligosaccharides. In the work presented herein, the disaccharide alphaFuc1-4GlcNAc is used as a scaffold toward the synthesis of a series of glycomimetic derivatives. Microcalorimetry and structural studies indicate that several of the derivatives are potent inhibitors of the lectin, with affinity in the same range as the best known natural ligand, Lewis a, and could represent interesting leads for the development of future antibacterial compounds.

Oligoarabinofuranosides 1−4, fragments of the arabinan components found in the mycobacterial cell wall have been synthesized. 1 and 2 are representative of the structural features of the internal core of arabinogalactan, arabinomannan and lipoarabinomannans. 3 is the capping motif of the lipoarabinomannan of Mycobacterium tuberculosis and M. bovis BCG while 4 is the hexasaccharide found at the non-reducing end of arabinogalactan. Complete stereocontrol was

The synthesis of oligomeric glycocomimetics has been performed for targeting the Pseudomonas aeruginosa PA-IIL lectin, which is of therapeutical interest for anti-adhesive treatment. The disaccharide alpha-L-Fucp-(1-->4)-beta-D-GlcNAc, which is a high-affinity ligand of the lectin, has been coupled to dimeric and trimeric linkers with various lengths and geometries. A series of linear dimers displayed an efficient clustering effect and a very strong affinity, with a lower dissociation constant of 90 nM. The trimeric compound was less efficient in inhibition assays but displayed high affinity in solution. Titration microcalorimetry and molecular modeling allowed in-depth analysis and rationalization of the binding data. These glycoclusters could act by crosslinking the lectins present on the surface of bacteria and therefore interfere with host recognition or biofilm formation.

The mycobacterial cell wall is a promising target for the development of new antituberculosis drugs. We report the synthesis and preliminary biological evaluation of imino sugar−oligoarabinofuranoside hybrids, a new class of mycobacterial arabinosyltransferase inhibitors. These hybrids were built from various chiral polyhydroxylated pyrrolidines (imino sugars) linked to small oligoarabinofuranosides. The coupling reaction was a reductive amination of a suitable oligoarabinofuranoside aldehyde with an unprotected amine